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Byline: Dillibabu. Ethiraj, Venkatraman. Indiran, Kannan. Kanakaraj, Prabakaran. Madhuraimuthu A 24-year-old woman came with complaints of upper abdominal swelling for the last 6 months, early satiety associated with loss of [...]

Many ectotherms regularly experience considerable short-term variations in environmental temperature, which affects their body temperature. Here we investigate the cardiovascular responses to a stepwise acute temperature increase from 10 to 13 and 16[degrees]C in rainbow trout (Oncorhynchus mykiss). Cardiac output increased by 20 and 31% at 13 and 16[degrees]C, respectively. This increase was entirely mediated by an increased heart rate ([f.sub.H]), whereas stroke volume (SV) decreased significantly by 20% at 16[degrees]C. The mean circulatory filling pressure (MCFP), a measure of venous capacitance, increased with temperature. Central venous pressure ([P.sub.ven]) did not change, whereas the pressure gradient for venous return (MCFP-[P.sub.ven]) was significantly increased at both 13 and 16[degrees]C. Blood volume, as measured by the dilution of [sup.51]Cr-labeled red blood cells, was temperature insensitive in both intact and splenectomized trout. This study demonstrates that venous capacitance in trout decreases, but cardiac filling pressure as estimated by [P.sub.ven] does not change when cardiac output increases during an acute temperature increase. SV was compromised as [f.sub.H] increased with temperature. The decreased capacitance likely serves to prevent passive pooling of blood in the venous periphery and to maintain cardiac filling pressure and a favorable pressure gradient for venous return. cardiac performance; cardiac preload; stroke volume; venous capacitance; [sup.51]Chromium doi: 10.1152/ajpregu.00884.2006

Arterial remodeling occurs in response to mechanical and neurohumoral stimuli. We hypothesized that veins, which are not exposed to higher pressures in hypertension, would demonstrate less active remodeling than arteries. We assessed remodeling with two standard measures of arterial remodeling: vessel morphometry and the expression/function of matrix metalloproteinases (MMPs). Thoracic aorta and vena cava from sham normotensive and DOCA-salt hypertensive rats (110 [+ or -] 4 and 188 [+ or -] 8 mmHg systolic blood pressure, respectively) were used. Wall thickness was increased in DOCA-salt vs. sham aorta (301 [+ or -] 23 vs. 218 [+ or -] 14 [micro]m, P < 0.05), as was medial area, but neither measure was altered in the vena cava. The aorta and vena cava expressed the gelatinases MMP-2, MMP-9, transmembrane proteinase MT1-MMP, and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemically, MMP-2 localized to smooth muscle in the aorta and densely in endothelium/smooth muscle of the vena cava. Western and zymographic analyses verified that MMP-2 was active in all vessels and less active in the vena cava than aorta. In hypertension, MMP-2 expression and activity in the aorta were increased (59.1 [+ or -] 3.7 and 74.5 [+ or -] 6.1 units in sham and DOCA, respectively, P < 0.05); similar elevations were not observed in the vena cava. MMP-9 was weakly expressed in all vessels. MTI-MMP was expressed by the aorta and vena cava and elevated in the vena cava from DOCA-salt rats. TIMP-2 expression was significantly increased in the aorta of DOCA rats compared with sham but was barely detectable in the vena cava of sham or DOCA-salt hypertensive rats. These findings suggest that large veins may not undergo vascular remodeling in DOCA-salt hypertension. matrix metalloproteinase; artery; vein doi: 10.1152/ajpheart.00900.2006.

The efficacy and safety of pretreating vein grafts is assessed with edifoligide for patients undergoing coronary artery bypass graft (CABG) surgery. Results reveal that while failure of at least 1 vein graft is quite common within 12 to 18 months after CABG surgery, edifoligide is no ore effective than placebo in preventing these events.

Gene transfer to vein gratis has therapeutic potential to prevent late graft failure; however, certain issues, including efficacy and safety, have hindered the clinical application of this treatment modality. Here, we report the successful and efficient gene transfer of plasmid DNA via ex vivo electroporation into veins as well as into vein grafts. Two approaches were used: one involved transluminal in situ gene transfer using a T-shaped electrode (the 'Lu' method), and the other was an adventitial ex vivo approach using an electroporation cuvette followed by vein grafting (the 'Ad' method). The Lu method was earned out at 10 V, with optimal gene transfer efficiency in the in situ jugular veins of rabbits, and transgene expression was observed primarily in endothelial cells. However, when these veins were grafted into the arterial circulation, no luciferase activity was detected; this effect was probably due to the elimination of the gene-transferred cells as a result of endothelial denudation. In contrast, optimal and satisfactory gene transfer was obtained with the vein grafts subjected to the Ad method at 30 V, and transgene expression was seen primarily in adventitial fibroblasts. Gene transfer of endothelial nitric oxide synthase cDNA to the vein graft via the Ad method successfully limited the extent of intimal hyperplasia, even under hyperlipidemic conditions, at 4 wk after grafting. We thus propose that the Ad method via ex vivo electroporation may provide a novel, safe, and clinically available technique for nonviral gene transfer to sufficiently prevent late graft failure. endothelial cell nitric oxide synthase; adventitia; endothelial cells; hyperlipidemia; plasmid

Reactive oxygen species (ROS), such as superoxide and [H.sub.2][O.sub.2], are capable of modifying vascular tone, although the response to ROS can vary qualitatively among vascular beds, experimental procedures, and species. Endothelin-1 (ET-1) induces superoxide production, which can be dismutated to [H.sub.2][O.sub.2]. The RhoA/Rho kinase pathway partially mediates ET-1-induced contraction and recently was implicated in superoxide-induced contraction. We hypothesized that [H.sub.2][O.sub.2], not superoxide, mediates venous ET-1-induced contraction. Rat thoracic aorta and vena cava contracted to exogenously added [H.sub.2][O.sub.2] (1 [micro]M-1 [micro]M) [maximum aortic contraction = 10 [+ or -] 3% of phenylephrine (10 [micro]M) contraction; maximum venous contraction = 85 [+ or -] 13% of norepinephrine (10 [micro]M) contraction]. (+)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632, 10 [micro]M), a Rho kinase inhibitor, significantly reduced venous [H.sub.2][O.sub.2]-induced contraction (15 [+ or -] 1% of control maximum) and reduced maximum ET-1-induced contraction by 59 [+ or -] 1%. However, neither the [H.sub.2][O.sub.2] scavenger catalase (100 and 2,000 U/ml) nor cell permeable polyethylene glycol-catalase (163 and 326 U/ml) reduced ET-1-induced contraction in the vena cava. The catalase inhibitor 3-aminotriazole (3-AT) also had no effect on maximal venous ET-1-induced contraction. Basal [H.sub.2][O.sub.2] levels were three times higher in the vena cava than in the aorta (vena cava, 0.74 [+ or -] 0.09 nmol [H.sub.2][O.sub.2]/mg protein; aorta, 0.24 [+ or -] 0.05 nmol [H.sub.2][O.sub.2]mg protein). ET-1 (100 nM) increased [H.sub.2][O.sub.2] in the vena cava but not in the aorta (vena cava, 154.10 [+ or -] 17.29% of control [H.sub.2][O.sub.2]; aorta, 83.72 [+ or -] 20.20%). Antagonism of either ETA or ETB receptors with the use of atrasentan (30 nM) or BQ-788 (100 nM), respectively, reduced ET-1 (100 nM)-induced increases in venous [H.sub.2][O.sub.2]. In summary, ET-1 increased [H.sub.2][O.sub.2] in veins but not arteries, and venous ET-l-induced [H.sub.2][O.sub.2] production was independent of the contractile properties of ET-1. venous contractility; reactive oxygen species

Direct communication between arteries and veins without intervening capillary beds is the primary pathology of arteriovenous malformations (AVMs). Although Notch signaling is implicated in embryonic arteriovenous (AV) differentiation, its function in the adult mammalian vasculature has not been established due to the embryonic lethality that often occurs in both gain- and loss-of-function mutants. We expressed a constitutively active Notch4, int3, in the adult mouse endothelium by using the tetracycline-repressible system to suppress int3 during embryo-genesis, int3 caused profound blood vessel enlargement and AV shunting, which are hallmarks of AVM, and led to lethality within weeks of its expression. Vessel enlargement, a manifestation of AVM, occurred in an apparently tissue-specific fashion; the liver, uterus, and skin were affected, int3-mediated vascular defects were accompanied by arterialization, including ectopic venous expression of ephrinB2, increased smooth muscle cells, and up-regulation of endogenous Notch signaling. Remarkably, the defective vessels and illness were reversed upon repression of int3 expression. Finally, endothelial expression of a constitutively active Notch1 induced similar hepatic vascular lesions. Our results provide gain-of-function evidence that Notch signaling in the adult endothelium is sufficient to render arterial characteristics and lead to AVMs. arterialization | Notch signaling | angiogenesis | vascular remodeling

The potential of natural dietary polyphenols in the treatment of vascular diseases originating from veins has been suggested in the literature. However, the mechanisms involved to explain the effects of polyphenols are not yet elucidated. Therefore, the aim of this study was to investigate the mechanisms by which polyphenols from red wine (Provinols) modulated contraction in human veins. We took advantage of a human model previously reported as a new tool for pharmacological research, using tissue-engineered techniques allowing the production of vascular media based exclusively on human smooth muscle cells. Thus human tissue-engineered vascular media (TEVM) were produced with cells originating from umbilical cord vein. TEVM were treated with either vehicle or Provinols. Results showed that treatment of TEVM with Provinols significantly potentiated the contractile responses induced by histamine and bradykinin. The potentiating effect of Provinols was not associated with an enhancement of histamine-induced increase in cytosolic calcium; rather, it implied the presence of a C[a.sup.2+]-independent signaling pathway. Pharmacological studies indicated that action of Provinols took place at the level of phospholipase [A.sub.2]-Rho-kinase pathway and was associated with an enhancement of myosin light chain kinase activity. These results, obtained using the human TEVM, bring new insights to explain the regulation of venous contraction by polyphenols. tissue engineering; veins; smooth muscle

Tumor necrosis factor (TNF)-[alpha] is implicated in development of restenotic and atherosclerotic vascular lesions, which are pathological processes involving both proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Human VSMCs were recently found to contain heterogeneous subpopulations. We therefore examined whether TNF has different effects on distinct subpopulations of VSMCs. With the use of cloning techniques, two stable subpopulations of VSMCs were isolated from human saphenous vein: spindle-and epithelioid-shaped smooth muscle cells (Sp- and Ep-SMCs, respectively). We found that TNF stimulated growth in Sp-SMCs but had a toxic effect on Ep-SMCs. TNF did not induce apoptosis in Sp-SMCs as determined by nuclear staining and cellular DNA electrophoresis. In contrast, the reduction of viability in Ep-SMCs was associated with induction of apoptosis as characterized by cellular DNA fragmentation and nuclear condensation. Higher levels of the TNF-R1 receptor subtype were detected in membrane preparations from Ep-SMCs than in membranes from Sp-SMCs. Activation of caspase-3 was also selectively induced in Ep-SMCs but not in Sp-SMCs. Cycloheximide, an inhibitor of protein synthesis, enhanced the toxicity of TNF in Ep-SMCs. This effect of cycloheximide was not seen in Sp-SMCs. The data presented here demonstrate for the first time that TNF either promotes growth or induces apoptosis in human VSMCs depending on phenotype. tumor necrosis factor-[alpha]; spindle; epithelioid; cycloheximide; atherosclerosis; stenosis

Leg venous compliance is a determinant of peripheral venous pooling during orthostatic stress such that high venous compliance could contribute to reduced orthostatic tolerance. We tested the hypotheses that 1) calf venous compliance is reduced during baroreceptor unloading, and 2) calf venous compliance is greater in women than men. Twelve men (27 [+ or -] 2 yr) and 12 women (25 [+ or -] 2 yr) were studied in the supine posture. Calf venous compliance was determined by inflating a thigh venous collecting cuff to 60 mmHg for 8 min and then decreasing cuff pressure at a rate of 1 mmHg/s to 0 mmHg. The slope of the pressure-compliance relation (compliance = [[beta].sub.1] + 2*[[beta].sub.2]*cuff pressure), which is the first derivative of the quadratic pressure-volume relation [([DELTA]limb volume) = [[beta].sub.0] + [[beta].sub.1]*(cuff pressure) + [[beta].sub.2]*[(cuff pressure).sup.2]] during the reduction in collecting cuff pressure, was used to assess venous compliance at baseline and during one-legged lower body negative pressure (LBNP; -50 mmHg). At baseline, calf venous compliance was 48% lower (P < 0.001) in women than men and decreased in men ([DELTA]-25 [+ or -] 8%; P < 0.05) but not women ([DELTA]1 [+ or -] 11%) during LBNP. Rhythmic ischemic handgrip ([DELTA]6 [+ or -] 9%) and cold pressor testing ([DELTA]-9 [+ or -] 7%) did not alter calf venous compliance in a subgroup of men (n = 6). These data indicate gender-dependent effects on calf venous compliance under conditions associated with low sympathetic outflow (i.e., rest) and high sympathetic outflow (i.e., LBNP). However, they cannot explain gender-associated differences in ortbostatic tolerance. veins; orthostasis; autonomic nervous system; baroreflex; blood pressure

Intravital microscopic methods were used to investigate the dose-dependent effects of bradykinin on leukocyte-endothelial cell interactions, formation of platelet-leukocyte aggregates and venular hemodynamics in rat mesentery. Results showed that the effects of bradykinin on leukocyte rolling and adhesion is highly concentration dependent. The mechanism of these effects was found to be dependent on the activation of bradykinin B2 receptors and was mediated by the formation of platelet-activating factor (PAF) and PAF-like lipids. The effects of bradykinin on venular erythrocyte velocity and blood flow were also concentration dependent.

We describe a new experimental methodology for visualizing three-dimensional structures in microscopic tubes under flow conditions. Through the use of microfabrication techniques, artificial venular bifurcations are constructed from glass tubes with semicircular cross sections (radius = 50 kO. Aqueous fluorescent solutions are infused into the tubes at flow rates of about 1 [[micro]liter]/min, a value comparable to blood flow in the microcirculation. The flow is imaged using a combination of confocal microscopy and three-dimensional image reconstruction software techniques. The quantitative accuracy of the experimental method is evaluated by measuring the 'separation surface,' a formation resulting from converging flows at a bifurcation. Details of the fabrication process, fluidics, confocal microscopy, image reconstructions, optical effects, and computations are described. We show the first three-dimensional visualization of a microscopic flow structure using confocal microscopy, and within certain limitations, quantitative agreement between the measured and computed positions of the separation surface.

Preferential homing of naive lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines, yet no chemokine has been shown to have either the expression pattern or the activities required to mediate this process. Here we show that a chemokine represented in the EST database, secondary lymphoid-tissue chemokine (SLC), is expressed in the high endothelial venules of lymph nodes and Peyer's patches, in the T cell areas of spleen, lymph nodes, and Peyer's patches, and in the lymphatic endothelium of multiple organs. SLC is a highly efficacious chemoattractant for lymphocytes with preferential activity toward naive T cells. Moreover, SLC induces firm adhesion of naive T lymphocytes via [Beta]2 integrin binding to the counter receptor, intercellular adhesion molecule-1, a necessary step for lymphocyte recruitment. SLC is the first chemokine demonstrated to have the characteristics required to mediate homing of lymphocytes to secondary lymphoid organs. In addition, the expression of SLC in lymphatic endothelium suggests that the migration of lymphocytes from tissues into efferent lymphatics may be an active process mediated by this molecule.

A model of the thermal behavior of an extremity, e.g., a finger, is presented. The model includes the effects of heat conduction, metabolic heat generation, heat transport by blood perfusion, heat exchange between the tissue and the large blood vessels, and arterio-venous heat exchange. Heat exchange with the environment through a layer of thermal insulation, depicting thermal handwear, is also considered. The tissue is subdivided into four concentric layers simulating, from the center outward, core, muscle, fat, and skin. Differential heat balance equations are formulated for the tissue and for the major artery and the major vein traversing the finger. These coupled equations are solved numerically by a finite-difference, alternating direction method employing a Thomas algorithm. The numerical scheme was extensively tested for its stability and convergence. This paper presents the model equations and results of the convergence tests, and shows plots of blood and tissue temperatures along the axis of the model for combinations of parameters including the effect of countercurrent heat exchange between the artery and the vein.

Inhibitory effects of 5-hydroxytryptamine (5-HT) on pial vein spontaneous rhythmic contractions (SRC) are similar to those of 5 methooxytryptamine (5-MT) and 5-carboxamidotryptamine (5-CT), indicating a receptor sybtype for cAMP synthesis mediation. 5-HT, 5-MT and 5-CT induced inhibitions of SRC were weakened in a concentration of methysergide. This was found from pharmacological in vitro tissue bath techniques. Pial arteries and veins from brains of thirty adult pig heads were used for this experiment.

Assay studies and physiological and hemodynamic measurements reveal the cumulative influence of mild hypertension and obesity on venous distensibility. Plethysmographic measurements of venous volume and blood flow in several subjects indicate maintenance of blood and stroke volume in obese individuals, confirming the damaging effects of obesity and hypertension on venous volume.

A comparison of the capability of P-,E-, and L-selectins to regulate leukocyte rolling in skin and striated muscles using antibodies against the selectins and analyzing the consequences through intravital fluorescence microscopy reveals that only P-selectin mediates the leukocyte rolling. Introduction of anti-P-selectin antibodies results in the complete elimination of baseline leukocyte rolling, while introduction of anti-E and-L antibodies has no such effect. The effects of P-selectin on leukocyte rolling are clearly seen in the two microcirculation models of leukocyte rolling in postcapillary venules.

The regulation of microcircular leukocyte rolling and adherence by different adhesion receptors was investigated. Erythrocyte velocity, vessel diameter, leukocyte adherence and leukocyte rolling velocity were the parameters characterized in cat mesenteric venules. Results indicate that the recruitment of rolling and adherent leukocytes at low venular shear rates were caused by different molecular determinants.

Byline: L. Lanzarini (), E. Lucca () Author Affiliation: () Department of Cardiology, IRCCS-Policlinico S. Matteo Hospital, Piazza Golgi, 2, 27100 Pavia, Italy, IT

Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep. Am J Physiol Heart Circ Physiol 279: H1166-H1171, 2000.--To study the regulation of the ductus venosus (DV) inlet in vivo, we measured the effect of vasoactive substances and hypoxemia on its diameter in nine fetal sheep in utero at 0.9 gestation under ketamine-diazepam anesthesia. Catheters were inserted into an umbilical vein and a fetal common carotid artery, and a flowmeter was placed around the umbilical veins. Ultrasound measurements of the diameter of the fetal DV during normoxic baseline conditions [fetal arterial [PO.sub.2] ([PaO.sub.2]) 24 mmHg] were compared with measurements during infusion of sodium nitroprusside (SNP; 1.3, 2.6, and 6.5 [micro]g [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]) or the [[Alpha].sub.1]-adrenergic agonist phenylephrine (6.5 [micro]g [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]) into the umbilical vein or during hypoxemia (fetal [Pa.sub.O2] reduced to 10 mmHg). SNP increased the DV inlet diameter by 23%, but phenylephrine had no effect. Hypoxemia caused a 61% increase of the inlet diameter and a distension of the entire vessel. We conclude that the DV inlet is tonically constricted, because nitric oxide dilates it but an [[Alpha].sub.1]-adrenergic agonist does not potentiate constriction. Hypoxemia causes a marked distension of the entire DV. circulation; hypoxia; nitroprusside; vein

Venous emptying mediates a transient vasodilation in the human forearm. Am J Physiol Heart Circ Physiol 279: H1007-H1014, 2000.--We tested the hypothesis that venous emptying serves as a stimulus for vasodilation in the human forearm. We compared the forearm blood flow (FBF; pulsed Doppler mean blood velocity and echo Doppler brachial artery diameter) response to temporary elevation of a resting forearm from below to above heart level when venous volume was allowed to drain versus when venous drainage was prevented by inflation of an upper arm cuff to ~30 mmHg. Arm elevation resulted in a rapid reduction in venous volume and pressure. Cuff inflation just before elevation effectively prevented these changes. FBF was briefly reduced by ~16% following arm elevation. A transient (86%) increase in blood flow began by ~5 s of arm elevation and peaked by 8 s, indicating a vasodilation. This response was completely abolished by preventing venous emptying. Arterial inflow below heart level was markedly elevated by 343% following brief (4 s) forearm elevation. This hyperemia was minor when venous emptying during forearm elevation had been prevented. We conclude that venous emptying serves as a stimulus for a transient (within 10 s) vasodilation in vivo. This vasodilation can substantially elevate arterial inflow. blood flow; vein; doppler ultrasound; venoarteriolar reflex

High endothelial venules (HEV) are specialized postcapillary venules found in lymphoid organs and chronically inflamed tissues that support high levels of lymphocyte extravasation from the blood. One of the major characteristics of HEV endothelial cells (HEVEC) is their capacity to incorporate large amounts of sulfate into sialomucin-type counter-receptors for the lymphocyte homing receptor L-selectin. Here, we show that HEVEC express two functional classes of sulfate transporters defined by their differential sensitivity to the anion-exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and we report the molecular characterization of a DIDS-resistant sulfate transporter from human HEVEC, designated SUT-1. SUT-1 belongs to the family of [Na.sup.+]-coupled anion transporters and exhibits 40-50% amino acid identity with the rat renal [Na.sup.+]/sulfate cotransporter, NaSi-1, as well as with the human and rat [Na.sup.+]/dicarboxylate cotransporters, NaDC-1/SDCT1 and NaDC-3/SDCT2. Functional expression studies in cRNA-injected Xenopus laevis oocytes showed that SUT-1 mediates high levels of [Na.sup.+]-dependent sulfate transport, which is resistant to DIDS inhibition. The SUT-1 gene mapped to human chromosome 7q33. Northern blotting analysis revealed that SUT-1 exhibits a highly restricted tissue distribution, with abundant expression in placenta. Reverse transcription-PCR analysis indicated that SUT-1 and the diastrophic dysplasia sulfate transporter (DTD), one of the two known human DIDS-sensitive sulfate transporters, are coexpressed in HEVEC. SUT-1 and DTD could correspond, respectively, to the DIDS-resistant and DIDS-sensitive components of sulfate uptake in HEVEC. Together, these results demonstrate that SUT-1 is a distinct human [Na.sup.+]-coupled sulfate transporter, likely to play a major role in sulfate incorporation in HEV. lymphocyte recirculation | L-selectin | sulfation | sulfate transporter

Byline: A. Argiris (1), J. Rademaker (1), M. Mahmud (1) Author Affiliation: (1) Department of Medicine, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003, U. S. A., IL Article note: Received: 2 August 1997 Accepted: 25 August 1997