Vascular Function In Humans Research Articles

Atrial natriuretic peptide regulates regional vascular volume and venous tone in humans.

To date, the contribution of basal atrial natriuretic peptide (ANP) levels to resting vascular function in humans is unknown. In the present study we sought to investigate the role of ANP in regulating regional vascular volume and venous tone in healthy subjects. We used radionuclide plethysmography to examine the effects of ANP and the ANP-receptor antagonist A71915 on forearm vascular volume. Creating pressure/volume relations, we determined changes in vascular volume, compliance, and tone. Performing dose-ranging studies, we additionally assessed the potency and specificity of A71915 in the forearm resistance vasculature. Equilibrium blood pool scintigraphy was then used to assess the effects of systemic administration of A71915 on regional intestinal vascular volume. Infusion of ANP increased forearm vascular volume in a dose-dependent manner (maximum 20%; P<0.001), exerting a maximum venodilating effect at plasma levels similar to that seen in heart failure. A71915 increased venous tone, thereby decreasing vascular volume by 9.6+/-1.1%, P<0.001 (forearm), and 2.6+/-0.5%, P=0.01 (intestinal beds). At an infusion ratio of 50:1, A71915 almost completely abolished the effects of ANP on forearm blood flow. ANP locally regulates regional vascular volume and tone without affecting compliance.

Mg 2+ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

In vitro studies with smooth muscle cells from rat aorta and dog cerebral blood vessels indicate that variation in free Mg 2+, within the pathophysiological range of Mg 2+ concentrations, found in human serum, causes sustained changes in membrane phospholipids and lipid second messengers. Incorporation of [ 3H]palmitic acid into phosphatidylcholine (PC) and sphingomyelin (SM) was altered within 15–30 min after modifying the extracellular Mg 2+ ion level ([Mg 2+] o). Decreased Mg 2+ produced a fall in both [ 3H]SM and [ 3H]PC over the first 2 h. After an 18-h incubation, the [ 3H]PC/[ 3H]SM ratio changed from about 20:1 to about 50:1. Increased [Mg 2+] o resulted in a 2- to 3-fold increase in [ 3H]SM compared to only a small increase in [ 3H]PC over the same period. There was a reciprocal relationship between [ 3H]ceramide and [ 3H]1,2-DAG levels with highest [ 3H]ceramide and lowest [ 3H]-1,2-DAG levels seen at lowest [Mg 2+] o. The results indicate that a fall in extracellular ionized Mg 2+ concentration produces a rapid and sustained decrease in membrane sphingomyelin and a moderate rise in intracellular ceramide. A major effect of lowering [Mg 2+] o appears to be a down-regulation of SM synthase. The increased membrane SM content and a concomitant decrease in cell ceramide, in the presence of elevated [Mg 2+] o, may be relevant to the apparent protective role of adequate Mg intake on vascular function in humans.

Vascular reactivity is impaired in genetic females taking high-dose androgens

Objective. To assess the vascular effects of high-dose androgen treatment in genetic females.Background. Male gender is an independent risk factor for coronary artery disease, suggesting either a protective effect of estrogens and/or a deleterious effect of androgens. We have recently demonstrated that androgen deprivation is associated with enhanced vascular reactivity in adult men, however, the effects of androgen excess on vascular function in humans has not been reported previously.Methods. We studied vascular reactivity in two groups of genetic females: 12 female-to-male transsexuals receiving long-term high-dose androgens, and 12 healthy female control subjects, matched for age and smoking history. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (leading to flow-mediated dilatation [FMD], which depends on normal endothelial function) and after sublingual nitroglycerin (NTG), an endothelium-independent dilator.Results. Testosterone levels were higher (15.2 ± 8.7 vs. 1.9 ± 1.3 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels were lower (1.2 ± 0.2 vs. 1.6 ± 0.4 mmol/L, p = 0.02) in the transsexuals compared with the control subjects. In each group, nine of 12 subjects were current or ex-smokers, leading to impaired FMD in both groups (5.1 ± 3.7% in the transsexuals vs. 6.9 ± 4.1% in controls, p = 0.28). The NTG response was significantly decreased in the transsexuals (15.9 ± 4.9% vs. 22 ± 5.8% in controls, p = 0.01), independent of the effects of age, cholesterol or vessel size.Conclusions. Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.

Abnormalities of vascular function in hyperhomocysteinaemia: relationship to atherothrombotic disease

Hyperhomocysteinaemia is a risk factor for atherothrombotic disease, but data are limited on the arterial histology in humans with hyperhomocysteinaemia, either with or without other risk factors. Studies in vitro and in animals have shown that hyperhomocysteinaemia, possibly by increasing oxidant stress as well as by other mechanisms, may induce dysfunction of the vascular endothelium and proliferation of vascular smooth muscle cells, both key processes in atherogenesis. In clinically healthy subjects with hyperhomocysteinaemia, endothelium-dependent vasodilation may be impaired, but endothelial antithrombotic and profibrinolytic function appear normal at this stage. In patients with atherosclerosis and hyperhomocysteinaemia, endothelial antithrombotic properties appear more severely impaired than in similar patients with normohomocysteinaemia. Controlled data on the effects of homocysteine-lowering treatment on vascular function in humans are not available. The increased risk of atherothrombotic disease conferred by hyperhomocysteinaemia may be related to homocysteine-associated impairments in endothelial and vascular smooth muscle cell function. The precise mechanisms by which homocysteine affects vascular cell function, however, are unknown.

Mg 2+ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis

Epidemiological studies associate low dietary magnesium intake with an increased incidence of ischemic heart disease and sudden cardiac death. We have used proton-magnetic resonance ( 1H-NMR) techniques and Mg 2+-selective electrodes to monitor changes in lipid extracts of aortic and cerebrovascular smooth muscle as extracellular ionized magnesium ion concentration ([Mg 2+] o) is lowered. We have found that, within the pathophysiological range of Mg 2+ concentrations, fatty acid chain length and double bond content are progressively reduced as [Mg 2+] o is lowered. In contrast, the plasmalogen content is progressively increased. A concomitant decrease in fatty acid chain length and double bonds indicates oxidation of double bonds resulting in truncation of the fatty acids. A decrease in lipid oxidation in the presence of elevated Mg 2+ could contribute to the apparent protective role of increased Mg 2+ intake on vascular function in humans.

In Vitro Responses of Human Peripheral Small Arteries in Hypercholesterolemia and Effects of Therapy

Studies in both animals and humans with raised lipid levels have demonstrated abnormalities in vascular function usually manifested by an impairment in endothelium-dependent vasorelaxation. This is believed to be an early event in atheroma formation. There are few data on the effects on vascular function in humans of lowering serum lipids. We conducted a study to investigate the effects of cholesterol reduction on the in vitro function of human peripheral small arteries in middle-aged patients with hypercholesterolemia. Subcutaneous gluteal fat biopsies were taken from 18 hypercholesterolemic (HC) patients (mean +/- SEM serum total cholesterol, 9.7 +/- 0.57 mmol/L) and 16 age- and sex-matched control subjects (mean cholesterol, 4.69 +/- 0.18 mmol/L). Subcutaneous small arteries (internal diameter, < 330 microns) were dissected and mounted on a wire myograph for isometric tension measurements. The HC patients showed impaired relaxation to acetylcholine (10(-9) to 10(-6) mol/L) after preconstriction with the thromboxane A2 analogue U46619 (10(-6) mol/L, mean maximum relaxation, 42.9 +/- 5.4%) compared with control subjects (85.7 +/- 4.0%, P < .00001). Incubation with the nitric oxide substrate L-arginine (3 mmol/L) improved the endothelium-dependent vasorelaxation response to acetylcholine (70.9 +/- 6.0%, P < .01) in patients but not in control subjects. Also, there was a smaller but significant difference in responses to the endothelium-independent agent sodium nitroprusside (10(-9) to 10(-6) mol/L) between the HC group (mean maximum relaxation, 76.9 +/- 6.0%) and the control subjects (89.7 +/- 6%; P < .01). A total of 10 patients had a second gluteal skin biopsy and repeat functional studies after successful cholesterol-lowering therapy after a mean period of 9.9 +/- 4.7 months. A significant reduction in total and LDL cholesterol was achieved (5.29 +/- 0.2 and 3.23 +/- 0.21 mmol/L, respectively; P < .001). This restored vasorelaxation to control values in response to both acetylcholine (mean maximum relaxation, 83.3 +/- 3.8%; P < .0001) and sodium nitroprusside (87.9 +/- 4.8%, P < .01). Although both groups were normotensive, there were significantly higher blood pressures in the HC group compared with control subjects (139 +/- 4.1 versus 123 +/- 3.0 mm Hg systolic, P < .01; 84 +/- 1.3 versus 75 +/- 2.2 mm Hg diastolic, P < .01). There was no difference in initial blood pressures between the entire group of 18 and the 10 patients who had repeat biopsies. The blood pressures fell to control values after cholesterol reduction (129.33 +/- 4.93 mm Hg systolic and 72.33 +/- 2.93 diastolic mm Hg, P < .02 relative to pretreatment values). These results demonstrate abnormalities of both endothelium-dependent and -independent relaxation in human peripheral small arteries that are normalized with effective lipid lowering. The changes in blood pressure may have been secondary to the improvement in vascular function.

Aging and microcirculatory dynamics in human gingiva

There have been no published reports characterizing gingival vascular function in humans of different ages. In this study, we compared gingival vascular dynamics in 60 healthy male humans ranging in age from 18-75 years (young, 18-25 years (Y); middle, 35-45 years (M); old, 65-75 years (O), 20 subjects/group). Both videomicroscopy of individual microvessels and laser doppler flowmetry were employed to assess marginal gingival circulation. Systemic cardiopulmonary parameters were monitored as controls. The number of gingival vessels visible in a microscopic field was higher and the number of microvessels exhibiting active flow was lower in M and O compared to Y. There were no differences among age groups in laser doppler flow values (tissue blood flow) or in red blood cell velocity in individual vessels. Although not statistically significant with age there was a trend towards decreasing blood flow velocity in both the laser doppler and videomicroscopic measurements. Blood pressure increased slightly with age. Peripheral oxygen saturation was lower in O compared to Y and M. No differences were seen in heart rate, respiratory rate or end-tidal carbon dioxide concentration. The changes in blood pressure and oxygen saturation were expected. The differences in numbers of visible vessels and the number of vessels with active blood flow may reflect the way the gingival microcirculation adapts with age to changing nutritional needs or to microbial and/or mechanical challenge.

Erythrocyte water, Na+-K+ cotransport, and forearm vascular function in humans.

We examined the relationships between erythrocyte (RBC) composition (Na+, K+, and water content) and ouabain-insensitive transports (Na+-K+ cotransport, Li+-Na+ countertransport) and forearm vascular hemodynamics under standardized basal conditions and during vasoconstriction (intra-arterial infusion of graded doses of norepinephrine and angiotensin II) and vasodilation (intra-arterial phentolamine and postischemic exercise). RBC water content correlated positively and significantly (r = 0.53, p = 0.001) with minimum forearm vascular resistance, a measure of vascular structural change, and negatively with maximal forearm blood flow (r = -0.55, p less than 0.001). Similar correlations with forearm vascular resistance and blood flow were observed under all experimental conditions. RBC Na+-K+ cotransport correlated positively and significantly (r = 0.43, p = 0.01) with the change in forearm blood flow produced by phentolamine, a functional measure of alpha-adrenergic tone, and was as strong an independent predictor of phentolamine-induced blood flow change as was arterial norepinephrine concentration. RBC Na+-K+ cotransport was also significantly positively correlated with residual forearm blood flow and resistance after phentolamine administration, where nonadrenergic influences predominate. RBC water correlated negatively with Li+-Na+ countertransport (r = -0.33, p less than 0.05) and Na+-K+ cotransport (r = -0.44, p less than 0.01). We propose that RBC water is a marker for a vascular structural property that contributes to vascular reactivity. RBC Na+-K+ cotransport seems to relate most strongly to the sympathetically mediated control of forearm blood flow and may also be linked to the intrinsic myogenic tone of the forearm vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)