Search

Background: Annexin A3 (Anxa3) is a member of the calcium-regulated, cell membrane-binding family of annexin proteins. We previously confirmed that Anxa3 is expressed in the endothelial lineage in vertebrates and that loss of anxa3 in Xenopus laevis leads to embryonic blood vessel defects. However, the biological function of Anxa3 in mammals is completely unknown. In order to investigate Anxa3 vascular function in mammals, we generated an endothelial cell-specific Anxa3 conditional knockout mouse model (Anxa3 f/f ;Tie2-Cre)., Results: Anxa3 f/f ;Tie2-Cre mice are born at Mendelian ratios and display morphologically normal blood vessels during development. However, loss of Anxa3 leads to artery-vein (AV) misalignment characterized by atypical AV crossovers in the postnatal and adult retina., Conclusions: Anxa3 is not essential for embryonic blood vessel formation but is required for proper parallel AV alignment in the murine retina. AV crossovers associated with Anxa3 f/f ;Tie2-Cre mice are similar to AV intersections observed in patients with branch retinal vein occlusion (BRVO), although we did not observe occluded vessels. This new Anxa3 mouse model may provide a basis for understanding AV crossover formation associated with BRVO., (© 2020 Wiley Periodicals, Inc.)

Perivascular adipose tissue (PVAT) releases numerous factors and adipokines with paracrine effects on both vascular structure and function. These effects are variable as they depend on regional differences in PVAT among blood vessels and vary with changes in adiposity. There is considerable evidence demonstrating an association between coronary PVAT and the development and progression of coronary artery disease, which is associated with inflammation, oxidative stress, angiogenesis, vascular remodelling and blood clotting. However, PVAT also has a protective role in vascular grafts, especially the no-touch saphenous vein, in patients undergoing coronary artery bypass. This beneficial influence of PVAT involves factors such as adipocyte-derived relaxing factor, nitric oxide (NO), leptin, adiponectin, prostanoids, hydrogen sulphide and neurotransmitters, as well as mechanical protection. This article aims to highlight and compare the dual role of PVAT in the development and progression of coronary atherosclerosis, as well as in increased graft patency. Different deleterious and protective mechanisms of PVAT are also discussed and the inside-outside signalling paradigm of atherosclerosis development re-evaluated. The bidirectional communication between the arterial and venous wall and their surrounding PVAT, where signals originating from the vascular wall or lumen can affect PVAT phenotype, has been shown to be very complex. Moreover, signals from PVAT also influence the structure and function of the vascular wall in a paracrine manner., Linked Articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc., (© 2017 The British Pharmacological Society.)

Purpose: Develop an MRI method to estimate skeletal muscle oxygen consumption (VO2 ) with dynamic exercise using simultaneous measurement of venous blood flow (VBF) and venous oxygen saturation (SvO2 )., Methods: Real-time imaging of femoral VBF using a complex-difference method was interleaved with imaging of venous hemoglobin oxygen saturation (SvO2 ) using magnetic susceptometry to estimate muscle VO2 (Fick principle). Nine healthy subjects performed repeated 5-watt knee-extension (quadriceps) exercise within the bore of a 1.5 Tesla MRI scanner, for test/re-test comparison. VBF, SvO2 , and derived VO2 were estimated at baseline and immediately (<1 s) postexercise and every 2.4 s for 4 min., Results: Quadriceps muscle mass was 2.43 ± 0.31 kg. Mean baseline values were VBF = 0.13 ± 0.06 L/min/kg, SvO2 = 69.4 ± 10.1%, and VO2 = 6.8 ± 4.1 mL/min/kg. VBF, SvO2 , and VO2 values from peak exercise had good agreement between trials (VBF = 0.9 ± 0.1 versus 1.0 ± 0.1 L/min/kg, R(2) = 0.83, CV = 7.6%; SvO2 = 43.2 ± 13.5 versus 40.9 ± 13.1%, R(2) = 0.88, CV = 15.6%; VO2 = 95.7 ± 18.0 versus 108.9 ± 17.3 mL/min/kg, R(2) = 0.88, CV = 12.3%), as did the VO2 recovery time constant (26.1 ± 3.5 versus 26.0 ± 4.0 s, R(2) = 0.85, CV = 6.0%). CV = coefficient of variation., Conclusion: Rapid imaging of VBF and SvO2 for the estimation of whole muscle VO2 is compatible with dynamic exercise for the estimation of peak values and recovery dynamics following exercise with good reproducibility., (© 2014 Wiley Periodicals, Inc.)

This study aimed to investigate relations between ease of venous palpation and various venous factors, and to elucidate characteristics of hardly palpable veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous palpation was scored from 0: impalpable to 3: well palpable. Venous factors, namely venous depth, elevation, area and minimal pressure that starts to collapse vein, were measured using an ultrasonography before and after tourniquet inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the venous area and venous palpation score. The four venous factors correlated significantly with venous palpation score with the following correlation coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to-collapse pressure (-0.220). The characteristics of hardly palpable veins were small size, deep location and little elevation. Although vasodilatation facilitated venous palpation, venous depth and elevation were also important and should be included in future studies in which vasodilatation methods are evaluated., (© 2014 Wiley Publishing Asia Pty Ltd.)

Optical techniques including fluorescence lifetime spectroscopy have demonstrated potential as a tool for study and diagnosis of arterial vessel pathologies. However, their application in the intravascular diagnostic procedures has been hampered by the presence of blood hemoglobin that affects the light delivery to and the collection from the vessel wall. We report a computational fluid dynamics model that allows for the optimization of blood flushing parameters in a manner that minimizes the amount of saline needed to clear the optical field of view and reduces any adverse effects caused by the external saline jet. A 3D turbulence (k - ω) model was employed for Eulerian-Eulerian two-phase flow to simulate the flow inside and around a side-viewing fiber-optic catheter. Current analysis demonstrates the effects of various parameters including infusion and blood flow rates, vessel diameters, and pulsatile nature of blood flow on the flow structure around the catheter tip. The results from this study can be utilized in determining the optimal flushing rate for given vessel diameter, blood flow rate, and maximum wall shear stress that the vessel wall can sustain and subsequently in optimizing the design parameters of optical-based intravascular catheters., (Copyright © 2014 John Wiley & Sons, Ltd.)

We present a global, closed-loop, multiscale mathematical model for the human circulation including the arterial system, the venous system, the heart, the pulmonary circulation and the microcirculation. A distinctive feature of our model is the detailed description of the venous system, particularly for intracranial and extracranial veins. Medium to large vessels are described by one-dimensional hyperbolic systems while the rest of the components are described by zero-dimensional models represented by differential-algebraic equations. Robust, high-order accurate numerical methodology is implemented for solving the hyperbolic equations, which are adopted from a recent reformulation that includes variable material properties. Because of the large intersubject variability of the venous system, we perform a patient-specific characterization of major veins of the head and neck using MRI data. Computational results are carefully validated using published data for the arterial system and most regions of the venous system. For head and neck veins, validation is carried out through a detailed comparison of simulation results against patient-specific phase-contrast MRI flow quantification data. A merit of our model is its global, closed-loop character; the imposition of highly artificial boundary conditions is avoided. Applications in mind include a vast range of medical conditions. Of particular interest is the study of some neurodegenerative diseases, whose venous haemodynamic connection has recently been identified by medical researchers., (Copyright © 2014 John Wiley & Sons, Ltd.)

Reasons for Performing Study: One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels., Hypothesis and Objectives: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies., Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3-kinase) and PD-098059 (to block MAP-kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min., Results: Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin-incubated and wortmannin-incubated rings., Conclusions: This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP-kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions., Potential Relevance: The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis., (© 2011 EVJ Ltd.)

A time-efficient method is described for in vivo venous blood T(1) measurement using multiphase inversion-recovery-prepared balanced steady-state free precession imaging. Computer simulations and validation experiments using a flow phantom were carried out to demonstrate the accuracy of the proposed method for measuring blood T(1) by taking advantage of the continuous inflow of fresh blood with longitudinal magnetization undisturbed by previous radiofrequency pulses. In vivo measurement of venous blood T(1) in the sagittal sinus was carried out in 26 healthy children and adults aged 7-39 years. The measured venous blood T(1) values decreased with age as a whole (P = 0.006) and were higher in females than males (P = 0.013), matching the expected developmental changes and gender differences in human hematocrit level. The estimated mean blood T(1) values were highly correlated with normal hematocrit levels across age and gender groups (Spearman's r = 0.93, P = 0.008). The longitudinal repeatability of this technique was 4.0% as measured by the within-subject coefficient of variation. The proposed multiphase inversion recovery-prepared balanced steady-state free precession imaging method is a feasible technique for fast (< 1 min) and reliable in vivo venous blood T(1) measurement and may serve as an index of hematocrit level in individual subjects.

The power of fMRI in assessing neural activities is hampered by inter-subject variations in basal physiologic parameters, which may not be related to neural activation but has a modulatory effect on fMRI signals. Therefore, normalization of fMRI signals with these parameters is useful in reducing variations and improving sensitivity of this important technique. Recently, we have shown that basal venous oxygenation is a significant modulator of fMRI signals and individuals with higher venous oxygenation tend to have lower fMRI signals. In this study, we aim to test the utility of venous oxygenation normalization in distinguishing subject groups. A "model" condition was used in which two visual stimuli with different flashing frequencies were used to stimulate two subject groups, respectively, thereby simulating the situation of control and patient groups. It was found that visual-evoked BOLD signal is significantly correlated with baseline venous T2 (P = 0.0003) and inclusion of physiologic modulator in the regression analysis can substantially reduce P values of group-level statistical tests. When applied to voxel-wise analysis, the normalization process can allow the detection of more significant voxels. The utility of other basal parameters, including blood pressure, heart rate, arterial oxygenation, and end-tidal CO(2), in BOLD normalization was also assessed and it was found that the improvement was less significant. Time-to-peak of the BOLD responses was also studied and it was found that subjects with higher basal venous oxygenation tend to slower BOLD responses., (2009 Wiley-Liss, Inc.)

The morphology and diameter of the milk vein of 29 healthy Swiss braunvieh cows and the velocity of blood flow through it was measured by colour Doppler ultrasonography before and 10 minutes after they had been sedated with 0.03 mg/kg xylazine. The milk vein was situated immediately under the skin. It had a diameter of 0.8 to 1.6 cm and valves were visible in the milk vein of 12 of the cows. The spectral display appeared as a broad band structure with a wave-like course. The Doppler measurement point was 0.4 to 0.8 cm from the body surface. The diameter of the vein and the blood flow velocity did not differ significantly before and after the cows were sedated. The mean (sd) diameter of the milk vein before they were sedated was 1.3 (0.3) cm. The mean maximum blood flow velocity before they were sedated was 45.4 (12.5) cm/second, the mean velocity was 33.5 (9.5) cm/second, and the mean minimum was 25.8 (11.6) cm/second. There were significant correlations between the blood flow velocities before and after the cows were sedated and between individual cow's blood flow velocities, with correlation coefficients ranging from 0.69 to 0.94.

Reasons for Performing Study: Endothelin-1 (ET-1) may be a key mediator in the pathogenesis of laminitis, but endothelin-mediated responses in the venous microcirculation of the equine foot have yet to be fully characterised., Objectives: To characterise the response of equine laminar veins to ET-1 and evaluate the ET-1 receptor subtypes that mediate this response., Methods: Small veins (150-500 microns) draining the equine digital laminae from healthy horses and ponies subjected to euthanasia at an abattoir were investigated using wire myography. Concentration response curves were constructed for ET-1 in the presence of ETA (BQ123) and ETB (BQ788) receptor antagonists, and L-NAME, a nitric oxide synthase blocker. The selective ETB receptor agonist BQ3020 was investigated alone and following incubation with L-NAME, with or without BQ788., Results: Endothelin-1 contraction of laminar veins was significantly inhibited by BQ123 but not by BQ788. In the presence of L-NAME, sensitivity of laminar veins to ET-1 was enhanced 4-fold, and further addition of BQ788 did not alter this increased sensitivity. BQ3020 induced no venoconstriction; however, in the presence of L-NAME, it caused contraction of veins with approximately 30% of the efficacy of ET-1. The action of BQ3020 in the presence of L-NAME was abolished by BQ788., Conclusions: Both ETA and ETB receptors are involved in the net tonic response to ET-1 in normal laminar veins. A population of ETB receptors may be present on the vascular endothelium and on smooth muscle of laminar veins, and the action of ET-1 at these 2 sites is likely to be approximately equal and opposite., Potential Relevance: Our results clarify the function of the ET-1 receptor subtypes in laminar veins from healthy horses. Further study of ET-1 receptors in laminitic horses is therefore warranted.

Continuous arterial spin labeling experiments typically use flow-driven adiabatic fast passage inversion of the arterial blood water protons. In this article, we measure the effect of magnetization transfer in blood and how it affects the inversion label. We use modified Bloch equations to model flow-driven adiabatic inversion in the presence of magnetization transfer in blood flowing at velocities from 1 to 30 cm/s in order to explain our findings. Magnetization transfer results in a reduction of the inversion efficiency at the inversion plane of up to 3.65% in the range of velocities examined, as well as faster relaxation of the arterial label in continuous labeling experiments. The two effects combined can result in inversion efficiency reduction of up to 8.91% in the simulated range of velocities. These effects are strongly dependent on the velocity of the flowing blood, with 10 cm/s yielding the largest loss in efficiency due to magnetization transfer effects. Flowing blood phantom experiments confirmed faster relaxation of the inversion label than that predicted by T(1) decay alone.

Background and Purpose: Coronary venous activity is modulated by endogenous and exogenous nitrovasodilators. The present study was to determine the role of protein kinase G (PKG) in the regulation of the basal tension and nitrovasodilator-induced relaxation of coronary veins., Experimental Approach: Effects of a PKG inhibitor on the basal tension and responses induced by nitroglycerin, DETA NONOate, and 8-Br-cGMP in isolated porcine coronary veins were determined. Cyclic cGMP was measured with radioimmunoassay. PKG activity was determined by measuring the incorporation of 32P from gamma-32P-ATP into the specific substrate BPDEtide., Key Results: Rp-8-Br-PET-cGMPS, a specific PKG inhibitor, increased the basal tension of porcine coronary veins and decreased PKG activity. The increase in tension was 38% of that caused by nitro-L-arginine. Relaxation of the veins induced by nitroglycerin and DETA NONOate was accompanied with increases in cGMP content and PKG activity. These effects were largely eliminated by inhibiting soluble guanylyl cyclase with ODQ. The increase in PKG activity induced by the nitrovasodilators was abolished by Rp-8-Br-PET-cGMPS. The relaxation caused by these dilators and by 8-Br-cGMP at their EC50 was attenuated by the PKG inhibitor by 51-66%., Conclusions and Implications: These results suggest that PKG is critically involved in nitric oxide-mediated regulation of the basal tension in porcine coronary veins and that it plays a primary role in relaxation induced by nitrovasodilators. Since nitric oxide plays a key role in modulating coronary venous activity, augmentation of PKG may be a therapeutic target for improving coronary blood flow.

The MR signal decay in gradient echo sequences includes signal loss due to spin dephasing caused by static magnetic field inhomogeneities. This decay can be calculated for different geometries of the susceptibility distribution, such as spheres, cylinders, or cylinder networks. In particular, the model of an infinitely long cylinder is a good approximation for single straight blood vessels. Blood oxygenation and blood volume fraction are important parameters, which influence the signal in a characteristic way. In this work the signal decays for a single cylindrical vessel were investigated and evaluated in simulations, phantom measurements as well as in vivo measurements of small single veins in the human brain by using a 3D multiecho gradient echo sequence. Good agreement between simulations and phantom experiments was obtained for different experimental settings. Based on the simulations, physiologically consistent values of venous blood oxygenation level, Y, were extracted from the in vivo measurements of different veins and volunteers (Y = 0.55 +/- 0.02). The methods ability to measure changes in venous blood oxygenation induced by carbogen breathing was demonstrated in one volunteer, where an increase from Y approximately 0.5 to Y approximately 0.7 was observed., (Copyright 2007 Wiley-Liss, Inc.)

Background: Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)) are important modulators of vascular tone. Preliminary data from our laboratory suggests that K(ATP) channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific K(ATP) opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative K(ATP) channel openers., Materials and Methods: Functional activity of K(ATP) channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established K(ATP) channel opener, acted as control., Results: KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation., Conclusions: We conclude that K(ATP) channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of K(ATP) channels and via activation of nitric oxide-dependent pathways.

Objective: To analyze the effects of uterine contractions on ductus venosus (DV) pulsatility during the first stage of labor., Methods: Twenty healthy women were examined. Measurements were taken at three stages of cervical dilatation (<4 cm, 4-7 cm and >or=8 cm) during and between contractions. Peak velocity during ventricular systole (S) and atrial contraction (A), pulsatility index for veins (DV PIV), ductus venosus index (DVI) and the S/A ratio were measured., Results: The DV was observed successfully in 16 cases. The mean S velocity did not change significantly (64 cm/s during and 65 cm/s between contractions). The mean A velocity decreased significantly from 35 cm/s measured between contractions to 29 cm/s during contractions (P<0.0001). The mean DV PIV and DVI were significantly higher during contractions (0.72 and 0.55) than between contractions (0.57 and 0.45) (P<0.0001). There were no significant differences in means between stages of cervical dilatation., Conclusion: Significant differences during and between uterine contractions can be observed in DV pulsatility during normal labor.

Background and Objective: beta2-Adrenergic receptors (beta2-ARs) are polymorphic. In vitro studies have shown that agonist-promoted down-regulation is enhanced for Arg16Gly and blunted for Gln27Glu beta2-AR variants; Thr164Ile beta2-ARs exhibit reduced responsiveness to agonist stimulation. Our objective was to determine whether beta2-AR polymorphisms affect beta2-AR-mediated venodilation in healthy subjects in vivo., Methods: We studied dilation of phenylephrine-preconstricted dorsal hand veins induced by terbutaline (50-1000 ng/min) using the Aellig hand vein technique in subjects homozygous for the 3 most common beta2-AR haplotypes (group A, Arg16Gln27Thr164 [wild type (WT)] [n = 10]; group B, Gly16Gln27Thr164 [n = 8]; and group C, Gly16Glu27Thr164 [n = 9]) and in 8 subjects heterozygous for Thr164Ile beta2-AR (group D) at baseline and after 2 weeks of treatment with oral terbutaline, 5 mg 3 times daily., Results: Terbutaline dose-dependently dilated hand veins; sensitivity to terbutaline was 2-fold higher in haplotype group A versus group B or C; maximal dilation, however, was not haplotype-dependent. In Thr164Ile subjects terbutaline sensitivity but not maximal dilation was 4-fold lower than in WT subjects. Long-term terbutaline treatment desensitized venous beta2-AR in a haplotype-dependent manner: The extent of desensitization (reduction in maximal venodilation) was largest for haplotype A, modest for haplotype B, and almost absent for haplotype C. Long-term terbutaline treatment also desensitized venous Thr164Ile beta2-AR; after terbutaline treatment, dose-response curves for terbutaline-induced venodilation were superimposable in WT and Thr164Ile beta2-AR subjects., Conclusion: beta2-AR-mediated dilation of human hand veins is influenced by the 3 most common beta2-AR haplotypes and blunted in subjects heterozygous for Thr164Ile beta2-AR. Long-term terbutaline treatment desensitizes venous beta2-AR in a haplotype-dependent manner, with haplotype A (Arg16Gln27Thr164) showing greater desensitization than haplotype B (Gly16Gln27Thr164), which shows greater desensitization than haplotype C (Gly16Glu27Thr164).

Background and Objectives: Activation of alpha 2 -adrenergic receptors regulates a broad spectrum of physiologic responses, including blood pressure (centrally and peripherally), sedation, analgesia, insulin release, renal function, cognition, and behavior. The purpose of this study was to explore systematically the local vascular responses in humans triggered by a highly selective alpha 2 -adrenergic agonist (azepexole [B-HT 933]) and whether such responses are dose-dependent or influenced by age, gender, or allelic variation at the drug's receptor., Methods: We evaluated dorsal hand vein vascular responses to the infusion of a wide spectrum of doses of azepexole, assessing any venodilation, as well as the maximal extent of venoconstriction (B max ) and the dose that produced a half-maximal effect (K d ), in 50 healthy normotensive adults of both genders and 4 ethnicities. Genomic deoxyribonucleic acid from the study subjects was evaluated at polymorphisms of the alpha 2B -adrenergic receptor gene (ADRA2B)., Results: We found previously unreported initial venodilation to low doses (10-100 ng/min) of azepexole, followed by progressive, intense venoconstriction to higher doses (200-100,000 ng/min) of the drug. Younger individuals (aged <30 years) had less venodilation than older individuals (aged >30 years) with low doses of azepexole but had a greater extent of venoconstriction at higher doses of azepexole (ANOVA, P = .001). Men had less venodilation than women with low doses of azepexole but greater venoconstriction with higher doses (ANOVA, P = .036). Several common polymorphisms (>10% minor allele frequency) at ADRA2B (insertion/deletion polymorphism [Glu 322-325 ], G-98C, C1182A, and C1776A) did not show an association with either B max or K d for the drug response. The A36G (Thr12Thr) synonymous single nucleotide polymorphism displayed a nonsignificant trend (P = .073) toward higher K d in A/G heterozygotes compared with A/A homozygotes., Conclusions: Local infusion into the human dorsal hand vein of a highly selective alpha 2 -adrenergic agonist, azepexole, produces biphasic responses, with venodilation at a low dose and intense venoconstriction at a higher concentration. These responses to azepexole show prominent differences as a function of age and gender but appear not to depend on common allelic variations at the ADRA2B receptor.

Objectives: The platysma myocutaneous flap offers a regional reconstruction option for relatively small soft tissue defects in the head and neck area. However, epidermolysis of its skin paddle with resultant fibrosis and tongue tethering has been documented. This has been attributed to arterial and/or venous vascular compromise. We investigated the venous drainage patterns of this flap in a cadaveric study., Study Design and Setting: We made selective Microfil dye injections into the external and internal jugular veins of 5 cadavers. A wide cervical flap was then raised, and anatomic dissection of the superficial and deep venous systems was performed to identify the dominant draining veins of the platysma flap., Results: Universally, small communicating veins from the internal jugular venous system were noted to drain the platysma flap anteriorly. The external jugular vein was noted to drain the flap posteriorly., Conclusions: Although it is difficult to preserve the anterior communicating veins with 180 degrees flap rotation, the results of this study suggest a possible benefit of external jugular vein harvest in continuity with the platysma flap. Further clinical studies are needed to assess whether flap venous congestion, epidermolysis, and resultant fibrosis can be minimized with this technique.

Assessment of drug-induced venodilation by the dorsal hand vein compliance method requires stable constriction of the vein. This study was designed to investigate intra- and intersubject reproducibility of the venous preconstriction technique in response to phenylephrine and prostaglandin F2 alpha and to determine the influence of basal vein size. Twelve healthy male nonsmokers participated in a prospective cross-over study. Inter- and intrasubject variability was tested in response to phenylephrine and PGF2 alpha on different study days in the same hand vein. The dose of the respective constrictor causing approximately 80% constriction of the vein (ED80) was determined and infused for another 100 minutes. Actual vein size was measured every 5 minutes. Coefficient of variation and regression analyses were performed to analyze influence of vessel size on ED80 of the respective constrictor. Adjusted constriction levels were stable and well reproducible in all subjects. The intersubject coefficient of variation of ED80 ranged from 0.9% to 6.7% for phenylephrine and from 0.9% to 6.9% for PGF2 alpha. Whereas responses to phenylephrine were independent of basal vein diameter, there was a positive correlation between ED80 of PGF2 alpha and basal vein size. Thus, the hand vein compliance method is a suitable method to study dilatory responses in phenylephrine- or PGF2 alpha-constricted veins with considerable interindividual but small intraindividual variability. However, in such studies, phenylephrine appears to be a more reliable tool than PGF2 alpha.

1 We investigated the adrenergic mechanisms of the two venous systems that drain the nasal mucosa, thereby their exact role in eliciting nasal decongestion. The action of endogenously released noradrenaline and exogenous adrenergic agonists on different segments of the nasal venous systems, i.e. collecting (LCV, SCV) and outflow (SPV) veins of posterior venous system, collecting (ACV) and outflow (DNV) veins of anterior venous system and venous sinusoids of the septal mucosa (SM), were studied. In vitro isometric tension of the vascular segments was measured. 2 Transmural nerve stimulation (TNS) produced constriction in ACV, DNV and SM, primary constriction followed by secondary dilatation in LCV and SCV and dilatation in SPV. Tetrodotoxin (10(-6) M) abolished all responses. Phentolamine (10(-6) M), prazosin (10(-6) M) and rauwolscine (10(-7) M) inhibited the constriction in all venous vessels. Propranolol (10(-6) M), atenolol (10(-6) M) and ICI 118,551 (10(-6) M) inhibited the relaxation in SPV but not in LCV and SCV. Phenylephrine and clonidine constricted whereas dobutamine and terbutaline relaxed all venous vessels dose-dependently. 3 These results indicate alpha(1)-, alpha(2)-, beta(1)- and beta(2)-adrenoceptors are present in both venous systems. TNS causes constriction of anterior venous system, venous sinusoids and posterior collecting veins primarily via postjunctional alpha(2)-adrenoceptors but relaxation of posterior outflow vein equally via postjunctional beta(1)- and beta(2)-adrenoceptors. The combined action of the two adrenergic mechanisms can reduce nasal airway resistance in vivo by decreasing vascular capacitance and enhancing venous drainage via the posterior venous system.

1. Deoxycorticosterone acetate (DOCA) salt hypertension is associated with an endothelin-1 (ET-1)-dependent increase in arterial resistance and mean circulatory filling pressure. Contraction of endothelium-intact arteries and veins from sham and DOCA-salt hypertensive rats to agonists of the ET(A) (ET-1((1-31))) and ET(B) receptor (sarafotoxin 6c; S6c) was investigated in tissue baths as was expression of mRNA for ET-1 and mRNA and protein for the ET(A) and ET(B) receptor. 2. ET-1((1-31)) contracted aorta and vena cava from sham rats with a 30 fold lower potency than ET-1. Contraction was not altered by the ET(B) receptor antagonist BQ788 (100 nM) but was abolished by the ET(A) receptor antagonist ABT-627 (30 nM). 3. In DOCA-salt thoracic aorta, maximum contraction to ET-1 and ET-1((1-31)) was reduced (36.6 +/- 6.3 and 13.3 +/- 4.4% of sham response, respectively); aorta did not contract to S6c. 4. In vena cava from DOCA-salt rats, contraction to ET-1 and ET-1((1-31)) was not reduced compared to sham contraction; vena cava from sham and DOCA-salt rats contracted to S6c with a similar potency. 5. Real time RT-PCR revealed that prepro ET-1 mRNA was increased 6.6 +/- 3.3 fold and 8.7 +/- 3.9 fold greater in DOCA-salt aorta and vena cava, respectively, compared to sham. Vena cava expressed a higher content of ET(A) and ET(B) receptor mRNA than aorta (P < 0.05), but no differences were observed between sham and DOCA-salt tissues. ET(A) and ET(B) receptor protein was identified in all tissues. Immunoreactive ET(A) receptor, observed as a 65, 30 and 28 kDa bands, was expressed 400% greater in DOCA-salt aorta compared to sham, but was not altered in vena cava. Immunoreactive ET(B) receptor, observed as 120, 45 and 30 kDa bands, tended to be higher in vena cava compared to aorta, but was not different in sham and DOCA-salt vena cava. 6. These results suggest that ET(A) receptor function is impaired in aorta but not vena cava of DOCA-salt rats. The ET(B) receptor was present in the aorta but, unlike in veins, does not mediate contraction directly. A sustained response to ET-1 in the venous circulation may contribute to the elevated blood pressure in the DOCA-salt model.

The presence of magnetic background field inhomogeneity (DeltaB) may confound quantitative measures of cerebral venous blood volume (vCBV) and cerebral oxygen extraction fraction (MR&#95;OEF) with T2*-based methods. The goal of this study was to correct its effect and obtain more accurate estimates of vCBV and MR&#95;OEF. A 3D high-resolution gradient echo sequence was employed to obtain DeltaB maps by two algorithms. The DeltaB maps were then used to recover the signal loss in images acquired by a 2D multiecho gradient echo / spin echo sequence. Finally, both quantitative estimates of MR&#95;OEF and vCBV were obtained from the DeltaB- corrected 2D multiecho gradient echo / spin echo images. A total of 12 normal subjects were studied. An overestimated vCBV was observed in the brain (4.29 +/- 0.78%) prior to DeltaB correction, while the measured vCBV was substantially reduced after DeltaB correction. Whole brain vCBV of 2.97 +/- 0.44% and 2.68 +/- 0.47% were obtained by the two different DeltaB correction methods, in excellent agreement with the reported results in the literature. Furthermore, when MR&#95;OEF was compared with and without DeltaB correction, no significant differences (P = 0.467) were observed. The ability to simultaneously obtain vCBV and MR&#95;OEF noninvasively may have profound clinical implications for the studies of cerebrovascular disease., (Copyright 2002 Wiley-Liss, Inc.)

The mechanism of alpha(2) adrenoceptor-mediated vasoconstriction is unknown, but may involve activation of voltage-sensitive calcium channels, and/or a protein tyrosine kinase. Recently the extracellular signal-regulated kinase (Erk) cascade, often an event downstream of tyrosine kinase activation, has been shown to mediate vasoconstriction to a variety of agents. The aim of this present study was to determine the involvement of the Erk signal transduction cascade in alpha(2) adrenoceptor-mediated vasoconstriction, and to confirm the involvement of activation of voltage-sensitive calcium channels, and protein tyrosine kinase. Contractions to the alpha(2) adrenoceptor agonist UK14304 in the porcine palmar lateral vein in vitro were reduced 70 - 80% by the MEK inhibitors PD98059 (10 - 50 microM) and U0126 (10 - 50 microM), indicating the involvement of the Erk signal transduction cascade. Immunoblots also demonstrated an increase in the phosphorylated (activated) form of Erk in palmar lateral vein segments after contraction with UK14304, which was inhibited by PD98059 and U0126. The calcium channel blockers nifedipine and verapamil, or removal of extracellular calcium inhibited UK14304-induced contractions and phosphorylation of Erk, demonstrating the importance of an influx of extracellular calcium. UK14304-induced contractions were inhibited by PP2 (1 - 10 microM), a selective inhibitor of Src tyrosine kinases, but not by PP3, an inactive analogue. PP2 also prevented the phosphorylation of Erk by UK14304. These data demonstrate that alpha(2) adrenoceptor-mediated vasoconstriction in the porcine palmar lateral vein is dependent upon activation of the Erk signal transduction cascade, which is downstream of an influx of extracellular calcium, and activation of Src tyrosine kinases.

The purpose of this report is to introduce a new computer model for the simulation of microvascular growth and remodeling into arteries and veins that imitates angiogenesis and blood flow in real vascular plexuses. A C++ computer program was developed based on geometric and biophysical initial and boundary conditions. Geometry was defined on a two-dimensional isometric grid by using defined sources and drains and elementary bifurcations that were able to proliferate or to regress under the influence of random and deterministic processes. Biophysics was defined by pressure, flow, and velocity distributions in the network by using the nodal-admittance-matrix-method, and accounting for hemodynamic peculiarities like Fahraeus-Lindqvist effect and exchange with extravascular tissue. The proposed model is the first to simulate interdigitation between the terminal branches of arterial and venous trees. This was achieved by inclusion of vessel regression and anastomosis in the capillary plexus and by remodeling in dependence from hemodynamics. The choice of regulatory properties influences the resulting vascular patterns. The model predicts interdigitating arteriovenous patterning if shear stress-dependent but not pressure-dependent remodeling was applied. By approximating the variability of natural vascular patterns, we hope to better understand homogeneity of transport, spatial distribution of hemodynamic properties and biomass allocation to the vascular wall or blood during development, or during evolution of circulatory systems., (Copyright 2001 Wiley-Liss, Inc.)

1. Urotensin-II (U-II) and its G-protein-coupled receptor, GPR14, are expressed within mammalian cardiac and peripheral vascular tissue and, as such, may regulate mammalian cardiovascular function. The present study details the vasoconstrictor profile of this cyclic undecapeptide in different vascular tissues isolated from a diverse range of mammalian species (rats, mice, dogs, pigs, marmosets and cynomolgus monkeys). 2. The vasoconstrictor activity of human U-II was dependent upon the anatomical origin of the vessel studied and the species from which it was isolated. In the rat, constrictor responses were most pronounced in thoracic aortae and carotid arteries: -log[EC(50)]s 9.09+/-0.19 and 8.84+/-0.21, R(max)s 143+/-21 and 67+/-26% 60 mM KCl, respectively (compared, for example, to -log[EC(50)] 7.90+/-0.11 and R(max) 142+/-12% 60 mM KCl for endothelin-1 [ET-1] in thoracic aortae). Responses were, however, absent in mice aortae (-log[EC(50)] <6.50). These findings were further contrasted by the observation that U-II was a 'coronary-selective' spasmogen in the dog (-log[EC(50)] 9.46+/-0.11, R(max) 109+/-23% 60 mM KCl in LCX coronary artery), yet exhibited a broad spectrum of vasoconstrictor activity in arterial tissue from Old World monkeys (-log[EC(50)]s range from 8.96+/-0.15 to 9.92+/-0.13, R(max)s from 43+/-16 to 527+/-135% 60 mM KCl). Interestingly, significant differences in reproducibility and vasoconstrictor efficacy were seen in tissue from pigs and New World primates (vessels which responded to noradrenaline, phenylephrine, KCl or ET-1 consistently). 3. Thus, human U-II is a potent, efficacious vasoconstrictor of a variety of mammalian vascular tissues. Although significant species/anatomical variations exist, the data support the hypothesis that U-II influences the physiological regulation of mammalian cardiovascular function.

The vertebrate vasculature develops in remarkably similar fashion in all vertebrates. A cohort of unspecified mesodermal cells differentiates into primitive endothelial cells, which migrate to and occupy positions within the stereotypical blueprint of the primitive vasculature. Once in position, these cells coalesce and form cords, which lumenize and become ensheathed by supporting pericytes and smooth muscle cells. This primitive vascular network is extensively remodeled in some places, and expanded by sprouting in others. Various studies using the mouse, quail/chick, and frog have uncovered a number of signals that guide these complex processes but many gaps still exist in our understanding of the mechanisms by which the embryonic vasculature is built. Because many questions will require in vivo studies to be properly addressed, the zebrafish, with its unique accessibility to analysis by combined embryological, molecular, and genetic methods, should prove invaluable in identifying new molecules involved in blood vessel development and integrating pathways that influence embryonic blood vessel formation.

In recent years, investigations of the venous vascular system have become increasingly important in the assessment of fetal myocardial function. The aim of the present Doppler ultrasound study was to establish both new reference ranges for blood flow velocity during the different phases of the cardiac cycle (S, SD, D, a) and various calculated indices ((S-a)/S, (S-a)/V(mean), (S-a)D, S/D, a/S, S/a) for the ductus venosus. Pulsed-wave colour Doppler was used in this prospective cross-sectional study to examine 696 women with low-risk pregnancies during the period from 14 to 41 weeks' gestation. Reference curves were constructed for the individual measuring parameters based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. A significant increase in blood flow velocity from 48 cm/s to 65.8 cm/s was observed during ventricular systole (=S) from 14 to 41 week's gestation. Similarly, increases in blood flow velocity were recorded during the endsystolic phase (=SD) (35.5 cm/s to 50.7 cm/s during early ventricular diastole (=D) (41.7 cm/s to 58 cm/s, p=0.0001) and atrial contraction (=a) (11.2 cm/s to 35 cm/s, p=0.0001), as well as for intensity-weighted mean velocity (30 cm/s to 48.3 cm/s). The venous indices were associated with significant decreases in the individual parameters with increasing gestational age: (S-a)/S from 0.77 to 0.47, (S-a)/V(mean) from 1.21 to 0.67, (S-a)/D from 0.89 to 0.54, S/a from 4.5 to 1.99. A significant increase from 0.23 to 0.53 was observed only for the quotient a/S. There were no changes in the S/D quotient (from 1.15 to 1.13). Regarding intra-observer reliability, more favourable results were obtained for calculated indices than for measurements of absolute blood flow velocities. At constant measuring conditions, the reference ranges established by this study for blood flow velocities and calculated indices in the ductus venosus may serve as the basis for Doppler ultrasound follow-up in a normal patient population as well as for the diagnosis of fetal myocardial insufficiency of hypoxic and congestive origin., (Copyright 2000 John Wiley & Sons, Ltd.)

Background: It has been suggested that topical glyceryl trinitrate (GTN) ointment may cause venodilatation and hence deter thrombophlebitis. However, objective evidence of an increase in vein diameter has not been demonstrated., Methods: B mode ultrasonography was used to measure arm vein diameter. In a prospective study, measurements were taken before and after 24 hours of exposure to topical GTN., Results: Reproducibility of vein diameter measurement was demonstrated. Basilic veins were larger than cephalic veins, but exposure to GTN ointment for 24 hours was not associated with measurable venodilatation., Conclusions: Ultrasonography enabled noninvasive measurement of intraluminal vein diameter. It is unlikely that GTN prevents thrombophlebitis in superficial arm veins by causing venodilatation.

Along with the jugular veins, the vertebral veins serve as an important pathway for venous blood returning from the brain. In this study, the authors report duplex sonographic findings in 138 healthy subjects without central nervous disease. Successful insonation was possible in 70.7% of all examined vessels. Bilateral insonation was achieved in 86 subjects (62.3%). Only 1 vertebral vein was detected in 23 persons (16.7%), whereas no vein was found in 29 persons (21%). The authors observed a marked variation of peak flow velocities ranged (5-81 cm/s, mean +/- standard deviation, 23.9 +/- 12.3 cm/s). No significant gender-related or side-to-side differences or age influences on flow velocities were detected. The authors' findings may be of relevance when discussing flow velocities in the vertebral veins in cases of cerebrovenous disorders (e.g., dural sinus thrombosis) or in patients after neck dissection.

Intermittent pneumatic compression has been established as a method of clinically preventing deep vein thrombosis, but the mechanism has not been documented. This study observed the effects of intermittent pneumatic compression of legs on the microcirculation of distant skeletal muscle. The cremaster muscles of 80 male rats were exposed, a specially designed intermittent pneumatic-compression device was applied to both legs for 60 minutes, and the microcirculation of the muscles was assessed by measurement of the vessel diameter in three categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed significant vasodilation in arterial and venous vessels during the application of intermittent pneumatic compression, which disappeared after termination of the compression. The vasodilation reached a maximum 30 minutes after initiation of the compression and could be completely blocked by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (10 micromol/min). A 120-minute infusion of NG-monomethyl-L-arginine, beginning coincident with 60 minutes of intermittent pneumatic compression, resulted in a significant decrease in arterial diameter that remained at almost the same level after termination of the compression. The magnitude of the decrease in diameter in the group treated with intermittent pneumatic compression and NG-monomethyl-L-arginine was comparable with that in the group treated with NG-monomethyl-L-arginine alone. The results imply that the production of nitric oxide is involved in the positive influence of intermittent pneumatic compression on circulation. It is postulated that the rapid increase in venous velocity induced by intermittent pneumatic compression produces strong shear stress on the vascular endothelium, which stimulates an increased release of nitric oxide and thereby causes systemic vasodilation.

Selective brain cooling (SBC) requires vasoactivity in the superficial veins of the face of the animal. This vasoactivity is possible because of an adequate amount of smooth muscle in the tunica media of each of these superficial vessels, enabling it to act as a "muscle sphincter". In this study, the angularis oculi, dorsal nasal, distal, and proximal parts of the facial veins in sheep were examined histologically to describe an anatomical basis for SBC. Measurements of the tunica media thickness, the lumen diameter, and the ratio of these measurements showed that the relative tunica media thicknesses in the angularis oculi vein and the dorsal nasal vein are statistically smaller (P < 0.001) than in the distal or the proximal parts of the facial vein. In the angularis oculi, dorsal nasal, and distal part of the facial vein, the tunicae mediae were composed of five to seven circularly arranged smooth muscle layers, suggesting their ability to vasoconstrict. The proximal part of the facial vein possesses both circularly and longitudinally arranged smooth muscle layers. The circular smooth muscle layers suggest a vasoconstrictory function, whereas the longitudinal smooth muscle layers suggest a vasoconstrictory function in this part of the facial vein. Both the dorsal nasal and the proximal part of the facial vein, but not the angularis oculi or the distal part of the facial vein, possess endothelial valves near their confluences with other veins. It was concluded from this study that the angularis oculi and the distal part of the facial vein vasoconstrict, whereas the proximal part of the facial vein vasodilates, enabling the necessary changes in blood flow in SBC.

Objective: Amiodarone, a class III antiarrhythmic agent, is a potent coronary vasodilator. However, direct evidence for its vasodilatory effects in human vasculature in vivo is not available. The aim of the study was to investigate the short-term effects of amiodarone in preconstricted human hand veins and to explore the underlying mechanisms., Methods: Thirty-one healthy male volunteers were studied with the use of the dorsal hand vein compliance technique. The hand veins of the subjects were preconstricted with the alpha 1-adrenergic receptor agonist phenylephrine, and amiodarone, inhibitors of nitric oxide formation (NG-monomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent potassium channels (glyburide [INN, glibenclamide]) were infused in the presence or absence of a cyclooxygenase inhibitor (acetylsalicylic acid), and the venodilator effect was measured. Furthermore, amiodarone was infused in prostaglandin F2 alpha (dinoprost)-preconstricted hand veins., Results: Amiodarone produced dose-dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced venodilation was lower in dinoprost compared with phenylephrine-preconstricted veins. Pretreatment with acetylsalicylic acid reduced the amiodarone-induced venodilation by 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decreased the venodilatory response of amiodarone by 31% +/- 11%, whereas only a slight but not statistically significant additional reduction in venodilation was detected after pretreatment with acetylsalicylic acid. Infusion of the solvents of commercially available amiodarone (polysorbate 80 and benzyl alcohol) did not cause vasodilation in phenylephrine-preconstricted veins., Conclusions: Amiodarone dilates preconstricted human hand veins in vivo and acts as a venodilator through the cyclooxygenase pathway, activation of nitric oxide synthase, and blockade of alpha adrenergic mechanisms.

The vascular system is a complex network transporting blood to and from all parts of the body. It distributes oxygenated and nutrient-rich blood to body tissue via arteries, arterioles, metarterioles, and capillaries. Venules and veins carry deoxygenated blood, cellular wastes, and carbon dioxide to the heart and lungs to be oxygenated or removed. The lymphatic system removes fluid left at the venous end of the capillaries and returns it to the circulatory system by way of the lymphatic ducts. Understanding the vascular system is basic to providing quality nursing care.

1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.

Background: Sympathetically mediated venoconstriction is augmented by exogenously administered angiotensin II. This study was designed to assess whether endogenous angiotensin II influences sympathetically mediated venous tone., Methods: Responses of dorsal hand veins to local intravenous administration of subsystemic doses of losartan, an angiotensin II type-1 receptor antagonist, were assessed with use of a well-validated displacement technique in eight healthy male volunteers. In a four-phase study, responses to local infusions of angiotensin II (4 to 64 ng/min) and norepinephrine (1 to 128 ng/min) or to sympathetic venoconstriction produced by a single deep breath were compared in the presence of either saline placebo or 30 microg/min losartan. Each phase of the study was conducted on a separate day, in random order, and each phase was separated by at least 1 week., Results: Angiotensin II (p = 0.03) and norepinephrine (p < 0.001) caused dose-dependent venoconstriction. Losartan attenuated the venoconstriction induced by angiotensin II (p = 0.048) but had no effect on the responses to norepinephrine or the venoconstriction induced by a single deep breath., Conclusions: In contrast to exogenously administered angiotensin II, basal endogenous angiotensin II does not influence sympathetically mediated venoconstriction in healthy humans. However, endogenous angiotensin II may have a role in circumstances of renin-angiotensin system activation, such as salt depletion.

This double-blind, placebo-controlled crossover study was designed to differentiate the pharmacodynamic effects of the angiotensin II receptor antagonist losartan from the angiotensin converting enzyme inhibitor enalapril. Effects of placebo, enalapril (10 mg), and losartan (20 and 100 mg) on local venous and systemic pressor responses to angiotensin I and II were compared in eight healthy male subjects. Treatments were administered orally approximately 4 hours before agonist infusions into a dorsal hand vein. Local changes in hand vein diameter and systemic blood pressure were monitored during the infusions. The 100 mg dose of losartan attenuated local venoconstrictor and systemic pressor responses to angiotensin I and II. In contrast, enalapril blocked only responses to angiotensin I. Both losartan and enalapril increased plasma renin concentration compared with placebo. These results are consistent with direct antagonism of angiotensin II receptors by losartan and with indirect effects of enalapril through inhibition of angiotensin converting enzyme.

1. The effects of the potassium channel opener, pinacidil, on mean arterial pressure (MAP), mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were studied in rats. 2. In pentobarbitone-anaesthetized rats given mecamylamine (ganglionic blocker, 3.7 micrograms kg-1) and noradrenaline (1.5 micrograms kg-1 min-1) to suppress autonomic reflexes, pinacidil (60 and 180 micrograms kg-1 min-1), relative to the vehicle, reduced MAP and TPR in a dose-dependent manner but did not significantly alter CO, MCFP or RV. 3. Pinacidil (10-300 micrograms kg-1 min-1) caused similar increases in MCFP, an inverse index of venous compliance, and similar dose-dependent reductions in mean arterial pressure (MAP) in conscious, intact rats and rats infused with the ganglionic blocker, hexamethonium (150 micrograms kg-1 min-1). In rats with vasomotor tone elevated by the infusion of noradrenaline (1.5 micrograms kg-1 min-1), pinacidil caused markedly greater depressor responses but did not significantly alter MCFP. 4. Our results show that pinacidil is an efficacious vasodilator of arterial resistance blood vessels but has little venodilator activity.

Isolated equine digital veins (EDVs) were used to study beta-adrenoceptor mediated vasodilation and to examine isoxsuprine's vasodilatory mechanism of action. When the blood vessel wall tension was raised with potassium chloride solution (KCl; 59 mmol/l), the order of vasodilator potency of beta-agonists was: isoprenaline > fenoterol > noradrenaline > dobutamine > isoxsuprine. The beta 2-selective adrenoceptor antagonist, ICI 118551 (1 nmol/l) caused a 6.74 and 6.65-fold parallel shift to the right in the dose response curves to fenoterol and noradrenaline respectively. Propranolol (10 nmol/l) inhibited the vasodilatory action of isoprenaline in a competitive manner (19.6 +/- 6.4-fold parallel shift to the right) but was much less effective as an inhibitor of isoxsuprine's vasodilatory action. Isoprenaline and fenoterol were just as effective as vasodilators when blood vessel wall tension was raised with KCl, the thromboxanemimetic U44069 (9, 11-dideoxy-9 alpha, 11 alpha-epoxymethano-prostaglandin F2 alpha; 30 nmol/l) or the alpha 1-adrenoceptor agonist, phenylephrine (0.3 mumol/l). In addition, fenoterol's relaxation of U44069-induced tone was competitively inhibited by the beta 2-selective adrenoceptor antagonist ICI 118551 (8.4 +/- 0.9-fold parallel shift to the right). By contrast, isoxsuprine was 81.9 times more potent as a vasorelaxant of phenylephrine-induced tone when compared with KCl-induced tone and proved completely ineffective as a vasodilator of U44069-induced tone. When dose response curves to alpha-adrenoceptor vasoconstrictor agonists were obtained in the presence of isoxsuprine (0.1 mumol/l), competitive antagonism occurred with methoxamine and noncompetitive antagonism with BHT-920. These data suggest EDVs possess beta 2-adrenoceptors mediating vasodilation. Isoxsuprine is an alpha 1-selective adrenoceptor antagonist but has very low potency and efficacy as a beta-adrenoceptor agonist in this functional bioassay. Indeed, much of the vasodilatory action of isoxsuprine may be due to a mechanism which does not involve beta-adrenoceptors.

The dorsal hand vein distention technique has been used to study the effects of alpha-adrenergic receptor antagonists on alpha-agonist-induced venoconstriction. Using this technique, we investigated the dose-effect relationships between different intravenous routes of phentolamine (an alpha-antagonist) administration on norepinephrine (an alpha-agonist)-induced hand vein constriction. Hand vein studies were done on healthy men; each man was studied on up to four occasions. On one occasion for each man, graded doses of phentolamine were infused into a hand vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED50) for reversal of venoconstriction, and the maximal reversal were calculated. On the other three occasions (randomly allocated) for each man, graded doses of norepinephrine were infused into a hand vein before and during intravenous infusions of (1) control (vehicle solutions); (2) systemic (other arm vein) phentolamine; and (3) local (hand vein) phentolamine. Systemic and local phentolamine dose ratios (ED50 of norepinephrine during phentolamine, divided by ED50 of norepinephrine before phentolamine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted hand vein) can completely reverse norepinephrine-induced venoconstriction. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fold) in responsiveness to norepinephrine-induced venoconstriction. To achieve comparable degrees of alpha-antagonism, however, systemic phentolamine must be administered intravenously at a dose approximately 3,000-fold higher than that of local phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibited vasorelaxant responses to both Cch and Bk whereas the cyclooxygenase inhibitor, ibuprofen (10 microM) had no inhibitory effect. The inhibitory action of L-NAME on the relaxations produced by Cch was partly reversed by L-arginine (3 and 10 mM). Cch-relaxations were potentiated in the presence of super oxide dismutase (15 units/ml) and inhibited by methylene blue (10 microM). The vasorelaxant effects of ATP (0.01 microM to 0.1 mM) were not dependent on the presence of the endothelium and the selective P2y receptor agonist, 2-methylthio-ATP proved to be ineffective as a vasodilator. Removal of the endothelium did not enhance the vasoconstrictor effects of the alpha 1 adrenoceptor agonist phenylephrine (0.01 microM to 0.1 mM) and treatment with L-NAME (300 microM) did not change the vasoconstrictor responses to 5-HT (1 nM to 10 microM) or the alpha 2 adrenoceptor agonist BHT-920 (1 nM to 1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

The venous system plays a pivotal role in volume and blood pressure homeostasis. We tested the hypothesis that the visco-elastic properties of the peripheral venous system are reduced in patients with (incipient) diabetic nephropathy. Twenty-two normotensive patients with long-term insulin-dependent diabetes mellitus (IDDM), 11 without and 11 with (incipient) nephropathy (eight microalbuminuria and three proteinuria, serum creatinine below 100 mumol l-1), and 14 healthy age/sex matched controls were studied. Forearm venous compliance (VENCOMP) was determined using strain gauge plethysmography and direct intravenous pressure measurements. Furthermore, the venodilatory effect of 0.4 mg sublingual nitroglycerin (NTG) was studied. In comparison with healthy controls, VENCOMP was decreased in patients without and with (incipient) nephropathy, without any differences between the two diabetic groups: 0.059 (0.052-0.066), 0.044 (0.038-0.059) and 0.049 (0.046-0.058) ml 100 ml-1 mmHg-1, respectively (medians and interquartile ranges) (P < 0.05). No differences in the increase of forearm volume after NTG were observed: 0.34 (0.11-0.51), 0.37 (0.19-0.50) and 0.39 (0.20-0.55) ml 100 ml-1, respectively. In conclusion, the visco-elastic properties of the peripheral venous system are reduced in patients with long-term IDDM. This reduction is not related to the presence of nephropathy. No major differences were observed in NTG-induced venodilation between diabetic patients and healthy subjects.

1. In the present study, responses of human omental small arteries and veins to endothelin-1 and endothelin-3 were characterized by use of the ETB receptor selective agonist, sarafotoxin S6c, the ETA receptor antagonist, BQ123, the ETB receptor antagonist, IRL1038, the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 300 microM) and indomethacin (10 microM). 2. Small arteries (internal diameter 413 +/- 22 microns) and parallel running veins (646 +/- 35 microns) were mounted in a myograph under a normalized tension equivalent to 90% of a transmural pressure of 100 mmHg and 19 mmHg in vivo, respectively. 3. In small arteries and veins, endothelin-1 caused a concentration-dependent increase in wall tension (Emax = 3.90 +/- 0.56 mN mm-1 and 1.90 m +/- 0.32 mN mm-1 respectively, P < 0.05) and was equipotent (arteries: pD2 = 8.91 +/- 0.11; veins: pD2 = 8.63 +/- 0.08, NS). In endothelium intact arteries, L-NMMA significantly enhanced the sensitivity to endothelin-1 (pD2 control: 8.92 +/- 0.16; pD2 L-NMMA: 9.37 +/- 0.11; P < 0.05). L-NMMA did not affect the sensitivity of veins to endothelin-1. Indomethacin was without effect in arteries and veins. In veins, endothelin-3 was about a hundred times less potent than endothelin-1 and showed a biphasic response curve. Small arteries did not contract to endothelin-3. Neither small arteries nor veins contracted to sarafotoxin S6c. Furthermore, no relaxation to endothelin-1 or sarafotoxin S6c was seen in any precontracted vessels. 4. BQ123 (0.03-3 MicroM) produced a concentration-dependent rightward parallel displacement of the endothelin-l concentration-response curve in small arteries and veins yielding pA2 values of 7.09 and 7.48 respectively. The slope of the Schild plot in arteries and veins was 1.26 +/- 0.24 (NS from unity) and 0.61 +/- 0.13 (P <0.05 compared to unity) respectively. IRL1038 (3 MicroM) did not affect the potency of endothelin-1 in arteries and veins. In veins, the low sensitivity component (pD2 = 7.16 +/- 0.08) of the biphasic response curve to endothelin-3 was completely blocked by BQ123 (3 MicroM), whereas the high sensitivity component (pD2 = 8.66 +/- 0.08) was resistant to BQ123 (3 MicroM) and IRL1038 (3 MicroM).5. These results indicate that contractions of human small vessels to endothelin-l are predominantly mediated by ETA receptors and that nitric oxide modulates the response to endothelin-l in small arteries but not in veins. The different antagonistic potency of BQ123 against endothelin-l and the differential endothelin-1/endothelin-3 potency ratios in arteries and veins provide evidence for the hypothesis that ETA receptors in human small arteries are different from ETA receptors in human small veins. There is no evidence of contractions mediated by 'classical' ETB receptors in these vessels, but small veins appear to contain a functional non ETA/non ETB receptor with a high affinity for endothelin-3.

Several methods have been employed in the study of bone perfusion. We used a method of determining inert gas wash-out by mass spectrometry in the study of blood flow rates in pigs. The method was validated by comparison of the result obtained with inert gas wash-out to that with measurement by microspheres. Furthermore, the effect of decreased inlet flow and venous congestion on the bone perfusion data was tested. The undisturbed bone blood flow was not significantly different when measured with wash-out of inert gas (7 +/- 0.7 ml/min/100 g) or with microspheres (9 +/- 2.9 ml/min/100 g), and the methods were correlated. Perfusion was reduced significantly, to 20% of the original value, after arterial occlusion. The changes in wash-out curves and accumulation of radioactive tracer provided substantial evidence for impaired intraosseous circulation following venous obstruction also. In conclusion, the study showed that this method of determining inert gas wash-out is feasible for studies of local perfusion rates in bone. The flow rates obtained by wash-out correlated well with the results of microsphere studies. In this animal model, both methods detected a fivefold reduction in flow rate after clamping of the arterial inflow. Obstruction of the venous outflow also impaired blood flow and lowered the cellular supply.

1. The roles of autofeedback and neuronal uptake in neurotransmission produced by electrical field stimulation in several rabbit isolated blood vessels were examined. 2. Blocking drugs were used to separate the possible purinergic and noradrenergic contributions to the end organ response: prazosin, antagonist at postjunctional alpha 1-adrenoceptors; rauwolscine and yohimbine, antagonists at pre- and postjunctional alpha 2-adrenoceptors; alpha,beta-methylene ATP, desensitizing agent at postjunctional P2x-purinoceptors. In addition to desensitizing postjunctional P2x-purinoceptors, alpha,beta-methylene ATP potentiated the noradrenergic component of the nerve-induced responses. 3. In the presence of an intact neuronal uptake mechanism, the vessels showed different contributions of purinergic (via P2x-purinoceptors) and noradrenergic (via alpha 1-adrenoceptors and alpha 2-adrenoceptors) components to the end organ response to nerve stimulation: saphenous artery (approximately equal contributions from P2x-purinoceptors and alpha 1-adrenoceptors), ileocolic artery (mainly P2x-purinoceptors with a smaller contribution from alpha 1-adrenoceptors), plantaris vein (mainly alpha 1-adrenoceptors with a small contribution from alpha 2-adrenoceptors and P2x-purinoceptors) and saphenous vein (alpha 1-adrenoceptors). 4. The presence of alpha 2-adrenoceptor-mediated autofeedback could be demonstrated for both purinergic and noradrenergic components of the nerve-induced responses in the artery preparations. In the veins, potentiation of nerve-induced responses by alpha 2-adrenoceptor antagonists could not be studied due to blockade of postjunctional alpha 2-adrenoceptor-mediated vasoconstriction. 5. Blockade of neuronal uptake with cocaine potentiated the noradrenergic component of the nerve-induced responses. Both alpha 1-adrenoceptor- and alpha 2-adrenoceptor-mediated components were potentiated, with a relatively greater potentiation of the alpha 2-adrenoceptor-mediated component. In the case of saphenous vein an alpha 2-adrenoceptor-mediated component which was previously absent was uncovered.6. Blockade of neuronal uptake with cocaine had no effect or reduced the purinergic component of responses, the latter effect presumably due to enhanced alpha 2-adrenoceptor-mediated autofeedback.7. In the presence of cocaine, nerve-induced responses in the saphenous vein were biphasic. Rauwolscine potentiated the first phase and inhibited the second phase thus demonstrating effects of pre- and postjunctional alpha 2-adrenoceptor-mediated activation in the same preparation.8. In conclusion, neuronal uptake and autofeedback processes play important and complex interacting parts in determining the relative contributions of alpha 1,- and alpha 2-adrenoceptors and P2.-purinoceptors in the end organ response to neurotransmission in blood vessels.

Potential differences in responsiveness of superficial veins from different regions to locally and systemically administered constrictor agents were investigated in healthy male volunteers. Compliance was determined by measuring venous diameter at a constant occlusion pressure. Dose-response curves for locally infused norepinephrine were established in five subjects on superficial hand and foot veins. Slopes of regression lines for norepinephrine log dose-response curves and doses required to produce equal reductions of diameter were virtually identical in both areas. In 12 subjects, 0.5 mg dihydroergotamine and placebo were administered intramuscularly in a double-blind randomized order; the venoconstrictor effect of dihydroergotamine was almost identical on hand and foot veins. Thus despite the marked differences in hydrostatic pressure to which they are exposed, superficial hand and foot veins react in a similar way to the constrictor agents investigated. The findings indicate that the responses of hand veins appear to be representative for superficial veins in other areas of the body.

The venous muscle pump function was quantitatively assessed through pregnancy weeks 16, 30, 38 and 3 months (week 53) following delivery, in 24 pregnant women who completed a normal pregnancy. A statistically significant increase was found in the mean venous reflux (P less than 0.01), which was restored to initial values postpartum. Expelled calf volume remained stable throughout pregnancy but increased following delivery. Venous outflow from the legs was significantly reduced in the third trimester. Subjective symptoms of venous insufficiency increased through pregnancy, but, these symptoms had virtually disappeared post partum, corresponding to the muscle pump normalization. No statistical correlation was found between venous muscle pump values and changes in hormone concentrations of estradiol, estriol and progesterone. It is suggested that venous insufficiency development in pregnancy is caused primarily by mechanical obstruction, or hormonal influence other than that of estradiol, estriol or progesterone. 17% (4.7-37%) of the women with a normal pregnancy developed a pathological venous muscle pump function.

1. Noradrenaline (NA), phenylephrine and UK-14304 elicited concentration-dependent contractions of the rabbit isolated ear vein of similar maximal magnitude. The rank order of potency, UK-14304 greater than noradrenaline greater than phenylephrine, is consistent with that of an effect mediated through an alpha 2-subtype. 2. The potent and highly selective alpha 1-adrenoceptor antagonists prazosin and YM-12617, at concentrations as high as 1 microM, produced less than a 4 fold rightward displacement of the NA concentration-response curve. 3. The selective alpha 2-adrenoceptor antagonists rauwolscine, Wy-26703 and CH-38083 antagonized responses to noradrenaline in a competitive manner. For all three antagonists, the pA2 values were consistent with an effect at alpha 2-adrenoceptors. However, 0.1 microM YM-12617 increased the potency of rauwolscine 2 fold indicating the presence of a small population of postjunctional alpha 1-adrenoceptors. 4. The relative antagonist potency of the yohimbine diastereoisomers rauwolscine and corynanthine against noradrenaline (rauwolscine 30 fold greater than corynanthine) is also consistent with an effect at alpha 2-adrenoceptors. 5. Contractions elicited by noradrenaline in the rabbit isolated ear vein appear to be mediated predominantly by postjunctional alpha 2-adrenoceptors.

Studies of substrate flux, isotope activity and metabolic balance frequently require arterial sampling. We evaluated: (1) whether substrate concentrations obtained from heated dorsal hand veins (HDHV) were comparable to samples obtained from the radial artery, (2) whether heat sufficient to arterialize HDHV altered contralateral forearm blood flow thus affecting flux calculations, (3) whether a +14 heating pad equaled a cumbersome +700 heating chamber, and (4) whether HDHV showed a dose-response curve to varying heat loads. In 12 normals, dorsal hand temperature was raised from 31.8 +/- 0.6 degrees C to 39.8 +/- 0.8 degrees C (chamber) and 39.3 +/- 0.3 degrees C (pad). Basal contralateral forearm blood flow (3.37 +/- 0.7 ml/100 ml tissue/min) was not significantly altered in the chamber (3.39 +/- 0.5 ml) or the pad (3.44 +/- 0.5 ml). Skin temperature of the unheated hand, an index of superficial blood flow (31.5 +/- 0.7 degrees C) did not change significantly in the chamber (31.6 +/- 0.7 degrees C) or the pad (31.2 +/- 0.7 degrees C). Forearm blood flow did not change with heating in eight postoperative patients. Comparative arterial and HDHV blood gases and 10 metabolic substrates from simultaneously drawn samples at various temperatures showed HDHV PO2 approached but did not equal arterial PO2 at temperatures greater than 39 degrees C. Glucose, amino acid, and substrate concentrations were comparable at 39 degrees C and did not change with increasing temperature. HDHV can reliably determine arterial substrate concentrations using an inexpensive heating pad. In cool environments (20-22 degrees C), contralateral forearm blood flow is not significantly altered. There is no benefit to heating the hand above 39 degrees C.

The effects of venous occlusion on the perfusion of porcine myocutaneous groin flaps were studied by means of the laser Doppler and the dermofluorometer. A consistent decrease in fluorometer readings following venous clamping with rebound to original or greater levels after unclamping was noted. A similar pattern was noted in laser Doppler studies. However, flow as measured by the Doppler remained significant (greater than 100 mV) even with venous outflow occlusion. It is hypothesized that the Doppler is more prone than the dermofluorometer to reflect non-nutritive flow in the flap during the early period following flap construction and, therefore, may be less accurate in the evaluation of actual flap microperfusion. The fluorometer was determined to be the more desirable instrument in monitoring the microcirculatory status of myocutaneous flaps during the immediate period after flap elevation and transposition.