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Although expansive remodeling of the maternal uterine circulation during pregnancy is essential for maintaining uteroplacental perfusion and normal fetal growth, the underlying physiological mechanisms are not well understood. Using a rat model, surgical approaches were used to alter uterine hemodynamics and wall shear stress (WSS) to evaluate the effects of WSS and venoarterial communication (e.g., transfer of placentally derived growth signals from postplacental veins to preplacental arteries) on gestational uterine vascular remodeling. Changes in WSS secondary to ligation of the cervical but not the ovarian end of the main uterine artery and vein provoked significant expansive remodeling at the opposite end of both vessels, but only in pregnant animals. The ≈50% increase in lumen diameter (relative to the contralateral horn) was associated with an upregulation of total endothelial nitric oxide (NO) synthase expression and was abolished by in vivo NO synthase inhibition with N-nitro-l-arginine methyl ester. Complete removal of a venous segment adjacent to the uterine artery to eliminate local venous influences significantly attenuated the WSS-induced remodeling by about one-half ( P < 0.05). These findings indicate that, during pregnancy, 1) increased WSS stimulates uterine artery growth via NO signaling and 2) the presence of an adjacent vein is required for arterial remodeling to fully occur. NEW & NOTEWORTHY This study provides the first in vivo evidence for the importance of venous influences on arterial growth within the uteroplacental circulation.

Background: The object of this work was to describe resistance to flow within a vein in a closed compartment., Methods: A vein is mathematically modeled as a collapsible cylinder with fixed perimeter exposed to extraluminal hydrostatic pressure within a closed compartment of the body. The principle of minimization of energy is used to determine the cross-sectional area and resistance to flow through such a cylinder in various states of collapse., Results: A mathematical expression for the cross-sectional area of a partially collapsed tube is derived. Resistance to flow is calculated within the tube in various states of collapse and compared with the resistance to flow in an annular tube of identical cross-sectional area. Resistance increases very rapidly in the first 5% of collapse and remains greater than that in an annular vessel of identical cross-sectional area through all further collapse. Resistance to flow closely follows a logarithmic gain as the tube undergoes collapse from extraluminal pressure until opposite sides of the vein make contact., Conclusion: Within a closed compartment in which there is rising pressure, resistance to flow through a vein is predicted to increase as a logarithmic function of the vein's cross-sectional area. This rapid rise in resistance and hence decline in flow are consistent with the position that in compartment syndromes of all anatomic locations, the venous contribution to resistance of flow is of paramount importance to the pathophysiology.

Purpose: We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling., Methods: Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively., Results: Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component., Conclusion: Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

In cats, the calcium antagonist Verapamil depressed vein constrictor responses to noradrenaline and angiotensine II both under conditions of wholesome endothelium and physical-chemical and chemical de-endothelisation. Following the de-endothelisation the vein responses recovered. The data obtained suggest that this recovery seems to be due to opening of new calcium channels that are independent of the Verapamil effect.

The paper generalizes unclear problems of venous return to the heart under different conditions. Data are presented on the venous return/cardiac output ratio, general peripheral resistance, arterial pressure and vascular bed capacity. A concept of double wave nature of formation of the circulation pressor systemic responses is advanced.

We investigated whether hypoxemia without acidemia affects ductus venosus (DV) blood velocity waveform pattern in sheep fetuses with intact placenta and whether worsening acidemia and impending fetal death are related to changes in DV velocimetry in fetuses with increased placental vascular resistance. A total of 34 fetuses were instrumented at 115-136/145 days of gestation. Placental embolization was performed in 22 fetuses on the fourth postoperative day, 24 h before the experiment. The control group was comprised of 12 fetuses with intact placenta. The experimental protocol consisted of fetal hypoxemia that was induced by replacing maternal inhaled oxygen with medical air. To further deteriorate fetal oxygenation and blood-gas status, uterine artery volume blood flow was reduced by maternal hypotension. Fetuses that underwent placental embolization were divided into two groups according to fetal outcome. Group 1 consisted of 12 fetuses that completed the experiment, and group 2 comprised 10 fetuses that died during the experiment. DV pulsatility index for veins (PIV) and fetal cardiac outputs (COs) were calculated. Placental volume blood flow, fetal blood pressures, and acid base and lactate values were monitored invasively. On the experimental day, the mean gestational age did not differ significantly between the groups. In groups 1 and 2, the baseline mean DV PIV and fetal COs were not statistically significantly different from the control group. In the control group, the DV PIV values increased significantly with hypoxemia. In groups 1 and 2, the DV PIV values did not change significantly, even with worsening acidemia and imminent fetal death in group 2. During the experiment, the fetal COs remained unchanged. We conclude that fetal hypoxemia increases the pulsatility of DV blood velocity waveform pattern. In fetuses with elevated placental vascular resistance, DV pulsatility does not increase further in the presence of severe and worsening fetal acidemia and impending fetal death.

This study examined the time course of changes in blood flow to the lower leg in response to venous distension--the veni-arteriolar vasoconstrictor response--in 31 healthy males. During a 5-min period of venous distension (thigh cuff pressure 50 mm Hg), calf blood flow (venous occlusion plethysmography) decreased more rapidly (within 30 s) compared to skin perfusion (after 2 min, Laser Doppler flowmetry), consistent with disparate filling times of superficial and deeper veins and a greater increase in deep vein volume. On completion of venous filling, vascular resistance in the skin was unchanged from baseline, implying that the reduction in perfusion was solely the result of reduced perfusion pressure. For the whole calf, vascular resistance was unchanged after 1 min but decreased thereafter by 35-45% from baseline, indicating adjustment of pre- or post-capillary resistances to maintain flow. Repeated plethysmographic flow measurements assisted the decrease in resistance, most likely by intermittent compression of the thigh cuff acting to displace blood volume centrally and alleviate congestion. These findings do not support an active veni-arteriolar vasoconstrictor mechanism in response to venous distension alone in the lower leg, and provide evidence of dynamic flow adjustments that should be acknowledged during procedures that involve prolonged periods of venous congestion.

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was approximately 62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only approximately 7%. Total venous compliance was found to be 21 times larger than arterial compliance (n = 3). Inferior vena caval compliance (0.32 +/- 0.015 ml x mmHg(-1) x kg(-1); mean +/- SE) was approximately 14 times the aortic compliance (0.023 +/- 0.002 ml x mmHg(-1) x kg(-1); n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance x windkessel pulse pressure; 7.8 +/- 1.1 ml) was only approximately 32% of the variation in aortic windkessel volume (24.3 +/- 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation.

Reliable differences in venous drainage and venous congestion and blood vessels filling of cerebral hemispheres in patients with vegetovascular dystonic and arterial hypertention who have suffered from Chernobyl accident have been detected by means of impedance tetrapolar plethysmography (rheoanalyzer PA5-01).

Non-invasive estimation of flow was investigated in an implantable rotary blood pump (iRBP) with a hydrodynamic bearing. The effects of non-pulsatile and pulsatile flows were studied using in vitro mock loops, and acute (N = 3) and chronic (N = 6) ovine experiments. Using the non-pulsatile and pulsatile mock loops an average flow estimation algorithm was derived from root mean square (RMS) pump impeller speed and RMS input power. These algorithms were programmed into the iRBP controller for subsequent validation in vivo. In the acute experiments, venous return and systemic vascular resistance were adjusted through pharmacological intervention and exsanguination to produce an average range of pump flows from 0.0 to 2.6 l min(-1). Over this range the RMS estimation error was 88 +/- 12 ml, with a linear correlation slope of 0.992 +/- 0.006 (R2 = 0.986 +/- 0.004). In the chronic experiments, animals were monitored daily for up to three months and an average range of flows from 2.8 to 4.8 l min(-1) recorded. A linear correlation between the estimated and measured pump flows yielded a slope of 1.005 +/- 0.006 (R2 = 0.966 +/- 0.004). The RMS estimation error was 120 +/- 11 ml. Using this algorithm it is possible to effectively estimate flow in a rotary blood pump without implanting additional invasive sensors.

We hypothesized that nitric oxide (NO) contributes to intrasplenic fluid extravasation by inducing greater relaxation in splenic resistance arteries than veins such that intrasplenic microvascular pressure (P(C)) rises. Fluid efflux was estimated by measuring the difference between splenic blood inflow and outflow. Intrasplenic infusion of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) (0.3 microg. 10 microl(-1). min(-1)) caused a significant increase in intrasplenic fluid efflux (baseline: 0.8 +/- 0.4 ml/min, n = 10 vs. peak rise during SNAP infusion: 1.3 +/- 0.4 ml/min, n = 10; P < 0.05). Intrasplenic P(C) was measured in the isolated, blood-perfused rat spleen. Intrasplenic infusion of SNAP (0.1 microg. 10 microl(-1). min(-1)) caused a significant increase in P(C) (saline: 10.9 +/- 0.2 mmHg, n = 3 vs. SNAP: 12.2 +/- 0.2 mmHg, n = 3; P < 0.05). Vasoreactivity of preconstricted splenic resistance vessels to sodium nitroprusside (SNP) (1 x 10(-12)-1 x 10(-4) M) and SNAP (1 x 10(-10)-3 x 10(-4) M) was investigated with the use of a wire myograph system. Significantly greater relaxation of arterioles than of venules occurred with both SNP (%maximal vasorelaxation: artery 96 +/- 2.3, n = 9 vs. vein 26 +/- 1.9, n = 10) and SNAP (%maximal vasorelaxation: artery 50 +/- 3.5, n = 11 vs. vein 32 +/- 1.7, n = 8). These results are consistent with our proposal that differential vasoreactivity of splenic resistance arteries and veins to NO elevates intrasplenic P(C) and increases fluid extravasation into the systemic lymphatic system.

In order to further our understanding of the physiology of corporal veno-occlusion, we developed a theory of a possible contribution to corporal venous outflow resistance which occurs as the result of venule stretching with resultant luminal narrowing when penile volume increases during the erection process. We stretched non-biological tubes and rabbit abdominal vena cava segments, performed flow-based and volume-based experiments to calculate the magnitude of N, the newly defined 'stretch-associated luminal constrictability' factor. We solved for (R(s)/R(u)), the ratio of the venule fluid resistance in the stretched state (R(s)) to the unstretched state (R(u)), to quantify the projected increases in fluid resistance as well as Q.R(u) where Q is the subtunical venule flow rate. For a given tube, N was found to be essentially constant for different amounts of stretch. A theory was formulated which predicted R(s) and Q as a function of N, DeltaP (intracavernosal pressure increase); V(E)/V(F) (tunical distensibility); X (cavernosal expandability) and R(u). Based on the magnitude of N=2, this theory predicts that patients with the highest values of both V(E)/V(F) and X would have maximal R(s) values, approaching infinity (complete occlusion) at a low DeltaP near 5 mmHg. In contrast, patients with low values of both V(E)/V(F) (eg Peyronie's disease) and X (eg corporal fibrosis), would be predicted to have minimal R(s) values. For example, a hypothetical patient with the lowest values of V(E)/V(F) and X would yield R(s) values only approaching 7.9 times that of unstretched values at a DeltaP increase of 90 mmHg. We concluded to that stretch-associated venule resistance may occur as a result of decreased sub-tunical venule diameter and increased sub-tunical venule length. In individual patients, stretch-associated venule resistance may either dominate or be a minor component of the overall mechanism of corporal veno-occlusion.

Few studies using human subcutaneous resistance arteries acknowledge the possibility of functional heterogeneity in these vessels. Large ( approximately 500 microm) and small (> or = 200 microm) resistance arteries (n=11) and veins (n=5) were identified using physical, structural and functional criteria in 14 biopsies of human gluteal fat. Endothelium-dependent relaxation was not evident in veins, while, unlike small resistance arteries (E(max) 95.74+/-1.86%; -log IC(50) 7.28+/-0.09), large resistance arteries with an intact endothelium failed to respond to acetylcholine. These results suggest that large resistance arteries may lack muscarinic receptors on the endothelium and emphasise the importance of careful vessel selection and characterisation in studies using human resistance arteries.

Altered beta-adrenergic regulation has been reported in individuals with hypertension. The variability in vascular responsiveness to beta-agonists, such as isoproterenol, observed in humans may be explained partially by beta(2)-adrenoceptor polymorphism. Individuals with the Gln27 form of the receptor may show reduced vascular reactivity because of downregulation expression of the receptor in the vasculature. We screened 127 normotensive white subjects, 37 of whom were homozygous for these alleles. Thirty-two subjects (17 Gln27 and 15 Glu27) agreed to receive brachial artery infusions of isoproterenol at doses of 1 to 300 ng. min(-1); forearm blood flow was measured by using venous occlusion plethysmography. Of these subjects, 25 (12 Glu27 and 13 Gln27) received local doses of isoproterenol (0.3 to 30.0 ng. min(-1)) via a dorsal hand vein preconstricted with norepinephrine. Compared with subjects homozygous for the Glu27 allele, subjects with the Gln27 substitution had lower baseline blood flow and, in response to isoproterenol, had a significantly attenuated increase in forearm blood flow. This pattern was more marked in veins. We also studied the relationship between the position 16 polymorphism and vascular reactivity. Homozygotes for Arg16 had significantly lower basal blood flow and attenuated increases in forearm blood flow compared with the Gly16 homozygotes. This was significant in veins but not in arteries. Thus, beta(2)-adrenoceptor genotype determines vascular responses to isoproterenol in forearm resistance vessels and in capacitance vessels. Further studies are necessary to establish whether beta(2)-adrenoceptor polymorphisms are important in the genesis of hypertension.

Rapid fluid administration is the cornerstone of successful trauma resuscitation of patients in a state of shock. Intravenous (IV) fluid delivery is a physical intrusion into a vein which results in a complex interaction between the rigid catheter and the compliant vein. We present an experimental model of IV infusion into a vein-like compliant tube that (a) demonstrated the interdependence between fluid administration and blood flow in a compliant tube and (b) allowed investigation of the contribution of the central venous system (between the infusion site and the heart) to the total resistance to infusion flow rate. The results show that in cases with very high resistance in the central venous system a significant increase of infusion flow rate cannot be achieved just by increasing the infusion pressure. Similarly, in cases of small veins when only small catheters can be used, infusate flow rate may be increased only by using two independent infusion ports. In cases with increased tissue pressure due to edema, gravity-driven infusion may not produce sufficient perfusion of the vascular compartments. It was also shown that the vein valves do not always close, and that peripheral blood flow may continue together with the infusate fluid (e.g., when there is a small downstream resistance and infusion with a small catheter).

The effects of pneumoperitoneum on peak venous flow velocity in the common femoral vein and the vena cava have already been studied. The results suggested that venous stasis occurs during surgical pneumoperitoneum. This study determines the effects of pneumoperitoneum on the overall venous outflow resistance of the lower limbs. Venous outflow resistance was measured during surgical procedures by impedance plethysmography in 12 patients undergoing laparoscopic cholecystectomy, 4 patients undergoing laparoscopic herniorrhaphy, 4 patients undergoing conventional cholecystectomy, and 2 patients undergoing conventional herniorrhaphy. Venous outflow resistance did not change significantly during laparoscopic cholecystectomy or herniorrhaphy. No difference in venous outflow resistance between laparoscopic cholecystectomy and herniorrhaphy was found. During pneumoperitoneum, no obstruction to total lower limb venous outflow could be demonstrated, indicating that venous stasis in the limbs did not occur, and consequently, flow in the iliac and inferior caval veins was not compromised. Hypothetically, active vasodilatation resulting from mild compression may explain this. In our view, no special measures to prevent deep venous thrombosis have to be taken during laparoscopic procedures.

1. We studied human lower limbs to test the hypothesis that the application of small cumulative venous congestion pressure steps is associated with a reduction in precapillary resistance. 2. Strain gauge plethysmography was performed on twenty-one young subjects (22.7 +/- 0.6 years). At each of the small cumulative pressure steps, limb blood flow was estimated from the initial slope of the volume response to transient (10 s duration) elevations of venous congestion pressure to 90 mmHg, after which the congestion pressure was returned to the previous value. The blood flow at each pressure was also expressed as a percentage of the initial control value. Peak tibial arterial blood flux was assessed, in four of the subjects, using colour duplex ultrasonography and the same congestion pressure protocol. 3. We used Darcy's Law to predict the limb arterial blood flow and blood flux at each venous congestion pressure, assuming that both mean arterial blood pressure and precapillary resistance remained constant. 4. The mean +/- S.E.M. control arterial blood flow at the lowest venous congestion pressure, 4.8 +/- 0.1 mmHg, was 2.77 +/- 0.18 ml min-1 (100 ml)-1. At the highest venous congestion pressure, 59.2 +/- 0.2 mmHg, arterial blood flow was 2.45 +/- 0.35 ml min-1 (100 ml)-1 (121.6 +/- 16.9% of the initial value). This did not differ significantly from the initial control value, but was significantly greater than the predicted value of 0.77 +/- 0.13 ml min-1 (100 ml)-1 (28.6 +/- 2.1% of the initial value) calculated assuming constant resistance and sustained mean arterial pressure. The tibial arterial peak blood flux at 58.3 mmHg venous congestion pressure was 102.2 +/- 2.3% of the control value, which was significantly greater than the predicted 17.2 +/- 1.3% of control, calculated for this pressure, assuming constant resistance and sustained mean arterial pressure. 5. Our data show that lower limb arterial blood flow is sustained when venous congestion pressure is raised using small cumulative steps, even at congestion pressures approaching mean arterial blood pressure. These data support the notion that precapillary resistance is influenced by signals generated at the microvascular and post microvascular levels and transmitted via the endothelium.

The effects of red blood cell aggregation on venous vascular resistance and conductance were examined in the cat lateral gastrocnemius muscle. During perfusion with blood of normal hematocrit, venous conductance fell linearly by 41% when blood flow was reduced from 5 to 1 ml x min(-1) x 100 g tissue(-1) and increased linearly by 155% when flow was increased from 5 to 20 ml x min(-1) x 100 g tissue(-1). This effect was not seen when the muscle was perfused with an acellular solution of 12% Dextran 40 in Ringer solution and was greatly reduced or absent with a nonaggregating suspension of red blood cells in Ringer solution + Dextran 40. Also, the venous vascular conductance at a control flow of 5 ml x min(-1) x 100 g tissue(-1) during perfusion with the nonaggregating red blood cell suspension was twice that with normal blood of the same hematocrit. The effect of flow on venous conductance was significantly reduced when red blood cell aggregation was increased by addition of Dextran 250 to the blood (200 mg/kg body wt) and was also reduced in animals with systemic hematocrit >50%. These findings suggest that red blood cell aggregation contributes importantly to venous vascular resistance in resting muscle.

Despite the well-established fact that the carotid sinus baroreflex system has profound control over the physical properties of the systemic circulation, the resistance to venous return (RVR) seems to be invariant of such control. We hypothesized that this apparent paradox may be explained from the baroreflex changes in systemic arterial compliance. In 12 pentobarbital-anesthetized mongrel dogs, RVR was measured at controlled carotid sinus pressures (CSP) of 50 and 200 mmHg with normal and artificially increased arterial compliance. Arterial compliance was determined from the arterial pressure decay when systemic blood flow was stopped with total vena caval occlusion. Changing CSP between 50 and 200 mmHg changed RVR significantly only under the condition of artificially increased arterial compliance. A four-parameter lumped model of the systemic circulation revealed that the baroreflex changes in arterial compliance and arterial resistance, which occurred in opposite directions, prevented a change in RVR when CSP was changed. The data also suggested that approximately 75% of RVR was attributed to large and conduit veins, the resistances along which were insensitive to baroreflex control. We concluded that the invariance of RVR results from a combination of 1) baroreflex change in the arterial compliance, 2) baroreflex insensitivity of the resistance along large and conduit veins, and 3) spatially distinct location between the major site of reflex change in capacitance and the major site of compliance.

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.

Intraluminal flow can cause both dilation or constriction of small arteries, depending on the level of tone. Both responses are specifically modulated in the same way by small changes in extracellular Na+ ([Na+]e). We have investigated the effect of changes in [Na+]e on the level of contraction induced by a standard flow of physiological salt solution in ring of segments of the rabbit facial vein and on the associated 45Ca2+ influx and net uptake. Decreasing [Na+]e by 20% reduced the response to flow by 58%, and increasing it by 20% augmented the flow response by the same extent. There is a linear relationship between the level of the flow-induced contraction and [Na+]e over the range 120-180 mM. An alteration in [Na+]e of 10 mM corresponds to a 20% change in flow-induced contraction. This relationship is quantitatively the same as that previously reported for the rabbit ear resistance artery [10]. Histamine (1 microM)-induced tone was not affected by changes in [Na+]e within the range 75-180 mM. 45Ca2+ influx and net uptake per unit force developed in response to flow were unaffected by these changes in [Na+]e. The flow-induced contraction of the vein was selectively, in comparison to that due to histamine, attenuated by amiloride, methyl-isobutyl-amiloride and monensin. It is argued that the observation that flow-induced contraction, caused by small alterations in extracellular sodium concentration, is not associated with changes in calcium uptake per unit force is consistent with an extracellular flow sensor.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between strength of short-term whole body autoregulation and peripheral resistance in the reference state (initial resistance) was investigated in 9 anesthetized closed-chest dogs and 18 anesthetized open-chest cats. Baroreflex regulation was abolished in one of three ways: barodenervation, ganglionic blockade, or setting pressure constant in the isolated carotid sinuses after vagotomy. Ascending aortic pressure and flow and venous pressure were measured in the reference state and 1-3 min after partial occlusions of the inferior vena cava. Cardiac output and peripheral resistance (ratio between arteriovenous pressure difference and cardiac output) were normalized for body weight. Strength of autoregulation was quantified by a resistance gain (Gra), defined as the ratio between change in normalized peripheral resistance and corresponding change in normalized cardiac output. A broad range of values for peripheral resistance in the reference state (Ro) was obtained as a result of the different interventions used to abolish baroreflex regulation. Arteriovenous pressure difference and normalized cardiac output during multiple vena cava occlusions in the 9 dogs and in 8 of the cats were fitted with a parabola convex to the flow axis. From the best fit, Gra was estimated. In the remaining 10 cats Gra was estimated from a single occlusion of vena cava. When data of all dogs and cats were taken together, we found a linear relationship between Gra and Ro: Gra = K1.Ro + K2. The constants K1 and K2 were 17.9 x 10(-3) min.kg.ml-1 and -14.5 x 10(-3) mmHg.min2.kg2.ml-2, respectively. The correlation coefficient was 0.9.

1. Venous resistance contributes very little to total peripheral resistance; more than half of the total blood volume, however, is contained in the extrathoracic veins. Owing to marked differences between venous and arterial anatomy and physiology, studies on veins and arteries usually require different methodological approaches. Whereas for arteries the most relevant parameters are resistance, pressure and flow, for veins volume and compliance are most important. For studies of general aspects of the peripheral circulatory system, venous occlusion plethysmography is probably the most useful method. The determination of both the rate of rise in limb volume and the total volume rise after inflating a proximally applied occlusion cuff to a subdiastolic pressure permits the concomitant estimation of both arterial flow and venous compliance. 2. Studies of direct pharmacological or physiological effects on veins, interactions of various pharmacological or physiological stimuli, or pathophysiological changes in venous responsiveness have been facilitated by the development of investigational techniques relying on direct measurements of the compliance of single human veins in vivo. One of these, relying on the use of a linear variable differential transformer (LVDT) for determining changes in the compliance of superficial veins at a standardized congestion pressure, has been found very suitable for the practical application in both patients and healthy subjects. 3. Physiological studies were carried out on the effect of age, exercise, temperature, and the menstrual cycle on venous compliance and venous responsiveness to various stimuli. In addition, interindividual variability in venous responsiveness in monozygotic and dizygotic twins and in unrelated subjects was investigated, and studies on the function of the endothelium were carried out in man in vivo. 4. Pathophysiological studies using this technique were reported from patients with hypertension, orthostatic hypotension, myocardial infarction, varicosis, cystic fibrosis, asthma, diabetes, systemic sclerosis, and cluster headache. 5. Clinical pharmacological studies represent a most important field for the use of this method. Studies were carried out on the effects of a large number of constrictor and dilator agents, and also on drug interactions on human veins in vivo. Venoconstriction was observed after local administration of alpha-adrenoceptor and 5-HT-receptor agonists, ergot derivatives, angiotensinogen, angiotensin I and II, and several prostaglandins. 6. Owing to the low venous tone present under effects can usually be quantified only on veins e.g. noradrenaline or 5-hydroxytryptamine. Under these conditions dilatation was observed after the administration of beta-adrenoceptor agonists, cholinergic (muscarinic) agonists, nitrates, calcium antagonists, bradykinin, substance P and several prostaglandins.

Objective: Our objective was to assess the effect of venous resistance in a clinically relevant range on flow rates through intravenous (i.v.) cannulae., Methods: Since resistances in series are additive, the sum of the resistance of the i.v. cannula and the vein equates to the total resistance to flow. Using resistance data from earlier work, the total resistance for various combinations of cannula and vein size was calculated, allowing a prediction to be made of the comparative flow rates between these combinations for a given driving pressure. Next, the clinical situation was simulated by measuring flow rates through i.v. cannulae connected in series to a variety of infusion devices with resistances known to be within the range of clinically relevant venous resistance., Results: The effect of venous resistance was greatest on large-bore cannulae, with significant reductions in flow occurring when even low levels of venous resistance were added. Throughout much of the range of venous resistances encountered clinically, total flows through two small-gauge cannulae exceeded that through a single large-gauge cannula., Conclusion: To achieve maximum benefit from a large-bore cannula, a suitably large vein must be chosen. Further, where venous access is difficult and high flow potential from an infusion system is required, two separate infusions through small cannulae may be a preferable option to a single large bore.

We examined the active and passive contributions of the alpha- and beta-adrenergic receptor mechanisms to the changes in systemic vascular capacitance caused by the carotid sinus baroreflex system in anesthetized, vagotomized dogs. The carotid sinuses were isolated from the systemic circulation and perfused with controlled pressures. To determine the changes in vascular capacitance, a constant flow, constant venous pressure cardiopulmonary bypass was used. The changes in unstressed vascular volume were calculated when carotid sinus pressure was reduced from 200 to 50 mmHg without any adrenergic receptor antagonist, with either an alpha- (phentolamine) or a beta- (propranolol) antagonist and then with both. The reflex change in unstressed vascular volume in the systemic circulation (22.6 +/- 9.0 ml/kg without any antagonist) was reduced by 72% with phentolamine, by 35% with propranolol, and by 73% with both antagonists. Our results suggest that the alpha-adrenergic mechanisms contribute significantly to active changes in systemic venous capacity. In addition, the beta-adrenergic system has very little effect on active changes in venous vessels but does contribute to the overall capacity changes by dilating the hepatic outflow resistance when the carotid sinus baroreflex system is activated.

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects of intravenous NG-monomethyl-L-arginine (L-NMMA) (3-25 mg/kg), an EDRF inhibitor, on mean circulatory filling pressure (MCFP) were determined in 10 awake instrumented rats. MCFP, the equilibrated systemic pressure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capacitance. L-NMMA caused a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L-NMMA on MCFP were reversed with L-arginine. In an additional four rats, in which hexamethonium was administered to induce ganglionic blockade, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as during the control unblocked state. These findings suggest that nitric oxide, which is likely EDRF, reduces baseline venous tone.

Sympathetically mediated changes in blood pressure are thought to occur through changes in arterial resistance (Ra). To test whether the critical closing pressure (Pcrit) could also play a role, we pump-perfused the vascularly isolated canine hindlimb at constant flow. Carotid sinuses were isolated and both vagus nerves cut. Carotid sinus (Pcar), arterial, perfusion (Pper), and venous (Pv) pressures and flow to the hindlimb (Q, electromagnetic flow probe) were measured. By decreasing pump flow to zero over time periods of 1-10 s and measuring the pressure at zero-flow, it was possible to estimate arterial compliance and Pcrit. Ra was calculated as (Pper - Pcrit)/Q. Venous resistance was calculated as (Pel - Pv)/Q, where Pel is the pressure in the compliant region obtained by the double-occlusion technique. Raising Pcar from 115 +/- 7 to 203 +/- 10 mmHg (n = 6) decreased Pcrit from 49.7 +/- 4.3 to 25.9 +/- 2.6 mmHg and Ra from 10.7 +/- 1.2 to 6.8 +/- 0.9 mmHg.min.100 g-1.ml-1 (P < 0.05). Lowering Pcar from 119 +/- 6 to 71 +/- 6 mmHg (n = 6) increased Pcrit from 37.0 +/- 3.3 to 61.0 +/- 8.5 mmHg and Ra from 10.0 +/- 1.6 to 14.0 +/- 2.4 mmHg.min.100 g.ml-1 (P < 0.05). Arterial compliance increased when Pcar was raised (P < 0.05) and decreased when Pcar was decreased (P < 0.1). Venous resistance did not change when Pcar was altered. In conclusion, changes in carotid sinus stimulation alters blood flow to the hindlimb through changes in both Pcrit and Ra.

The mechanical properties of isolated human oesophageal submucosal veins were investigated. The veins were without tone or spontaneous activity and possessed a high compliance, tolerating a stretch of several hundred per cent of the length at which the vessels were first able to contract with only minor increases in passive tension. The veins were capable of producing active tension when the length exceeded 30% of L0 (the length at which maximum wall tension (T0) was developed when activated by 124 mM K(+)-solution). The veins from the oesophageal body (OB) had a higher L0 than the veins from the gastrooesophageal junction (GOJ) (1180 microns vs 820 microns) and T0 was correspondingly higher (1.1 mN/mm vs. 0.6 mN/mm). However, there was no significant difference in the calculated effective transmural pressure (P) at the two locations. Noradrenaline induced contractions in all preparations tested with a maximum response equivalent to the tension achieved after stimulation with 124 mM K(+)-solution, pD2 values for noradrenaline in vessels from the oesophageal body and the gastroesophageal junction were 7.03 +/- 0.28 (mean +/- SEM) and 7.15 +/- 0.20, respectively. The present model seems suitable for future studies of human oesophageal submucosal veins from the oesophageal body and the gastrooesophageal junction.

The role of endothelium-derived nitric oxide in the regulation of vascular resistance (tonus) in cat skeletal muscle was studied with the use of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide formation from L-arginine. The study was performed with a whole-organ technique which permits simultaneous, continuous and quantitative recordings of resistance reactions in the whole vascular bed (RT) and in its three consecutive sections: large-bore arterial resistance vessels (greater than 25 microns; Ra,prox), small arterioles (less than 25 microns; Ra,micro) and veins (Rv). NG-monomethyl-L-arginine (3-100 mg kg-1 tissue, i.a.) induced a dose-dependent increase in resistance that was preferentially, but not selectively, confined to the large-bore arterial resistance vessels. At a maximally effective dose (100 mg kg-1), the nitric oxide inhibitor caused a marked constriction, within 5 min, on average increasing RT by 99%, Ra,prox by 138%, Ra,micro by 18% and Rv by 23%. The constrictor response to NG-monomethyl-L-arginine was long-lasting but disappeared gradually over a period of about 1 h. However, it could be abruptly abolished by excess L-arginine (300 mg kg-1, i.a.). The vasodilator response (RT) to acetylcholine was significantly attenuated in the presence of NG-monomethyl-L-arginine compared with the control response. The results suggested that nitric oxide formation from L-arginine by the vascular endothelium plays a fundamental role in the regulation of vascular resistance (tone) in vivo, with its main site of action located in the large-bore arterial resistance vessels.

Infusion of saline into the lumen of a resistance artery from the rabbit ear at rates between 0.5 and 20 microliters/min causes a rate-dependent maintained contraction. This contraction is independent of the direction of saline flow and of the endothelium. The contraction is prevented by pretreatment with the vasodilator papaverine (0.1 mM), which also reversed the contraction during flow. Exclusion of calcium from the physiological saline solution plus ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) prevents the contraction, as does pre-exposure to cobalt (1 mM) and manganese (1 mM). Both these ions depress saline flow contraction once it is established. Saline flow-dependent contraction changes in a complex manner with temperature. It is greatest in resistance arteries from the pial, ear (skin), and femoral (muscle) segments, moderate to poor in coronary, mesenteric, and renal segments, and absent in the pulmonary segments. A small ear vein adjacent to the ear resistance artery also contracts to saline infusion. Although an explanation based on the washout of a vasodilator metabolite cannot be excluded, we favor the hypothesis that saline flow-induced shear stress of the inner surface of the vessel wall mechanically activates the vascular smooth muscle cells causing an extracellular Ca2(+)-dependent contraction. This response takes place through indomethacin-insensitive calcium-dependent mechanisms in vascular smooth muscle that differ from those associated with commonly studied surface receptors and with stretch.

The effect of endurance training on reflex venomotor control during an orthostatic challenge was investigated in 11 sedentary male volunteers. An exercise (E) group (n = 6) underwent 12 weeks of endurance exercise training, whereas a control (C) group (n = 5) remained sedentary. Training significantly increased VO2max values in E (pre-training: 37.0 +/- 2.5 ml.kg-1.min-1; post training: 44.6 +/- 2.5 ml.kg-1.min-1), while C showed no significant change. During exposures to two levels of lower body negative pressure (-10 and -40 mm Hg), both C and E groups showed similar graded decreases in forearm venous volume (FVV). The magnitude of the FVV decreases did not differ between groups or when comparing pre-training and post-training values. We conclude that the reflex venoconstrictor response to LBNP was not affected by endurance training.

In twelve healthy volunteers given nitroglycerin sublingually (1.6 mg) or epicutaneously (12 mg), venous distensibility was found to be maximal, even at low plasma concentrations (less than 0.2 ng/ml); there was no further change with increasing concentrations. Peripheral arterial resistance, on the other hand, decreased progressively with rising plasma concentrations and no distinct plateau was demonstrable, even at the highest plasma concentration measured (greater than 2.0 ng/ml).

Magnetic resonance (MR) imaging of periodic engorgement of the erectile tissue surrounding the turbinates in the beagle dog yields remarkably quiet data that are well fitted by a single sinusoidal wave form. This observation holds in spite of right-left asymmetries in the distribution of the MR signal. The nasal cycle also occurs normally in humans. Judging from the clarity of its MR representation in the dog, it is possible that this phenomenon could be confused in human MR with upper respiratory congestion associated with pathological processes.

The low-viscosity bolus method was used to determine the longitudinal distributions of vascular resistance and intravascular pressure with respect to cumulative vascular volume from the lobar artery to the lobar vein in isolated dog lung lobes near functional residual capacity under zone 3 conditions. We found that the resistance distribution had two modes, a larger one upstream and a smaller one downstream from a local minimum. Over the range of vascular pressures studied the total vascular resistance decreased and the vascular volume increased with increasing vascular pressure. However, the shape of the normalized resistance distribution was independent of vascular pressure. Comparisons of the resistance distributions with the distributions of arterial, capillary, and venous volumes suggest that the modes represent regions of relatively high resistance proximal and distal to the capillary bed. These results are consistent with the concept that within the lobar vascular bed the highest resistance per unit blood volume is in the smallest arteries and veins, as suggested by morphometric data from other sources.

1. The aortic arch and both carotid sinuses were vascularly isolated and perfused. A hind limb was vascularly isolated and blood was pumped at constant flows into the femoral artery and the central end of a superficial metatarsal vein. 2. Large increases in aortic arch pressure resulted in decreases in arterial blood pressure, heart rate and femoral arterial perfusion pressure. The average response of the vein was a decrease of 11% in the pressure gradient between the perfused vein and the femoral vein. Similar responses were obtained when carotid sinus pressure was increased. 3. Crushing or cooling the lumbar sympathetic trunk caused responsed similar to those induced by increasing baroreceptor perfusion pressure. Stimulation at 1 HZ resulted in venous responses four times as great as the average reflex response, whereas frequencies of 2-5 Hz were required to produce changes in arterial resistance as great as those induced reflexly. 4. These experiments indicate, that although the large superficial veins of the dog's hind limb participate in the baroreceptor reflexes, the activities in the nerves supplying arterioles and veins must have been different.