How to assess endothelial function in human blood vessels.
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Cardiology↗
Biomedical subjects
J M Ritter
Publications and source records attributed to J M Ritter.
Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse.
The digital volume pulse can be recorded simply and noninvasively by photoplethysmography. The objective of the present study was to determine whether a generalized transfer function can be used to relate the digital volume pulse to the peripheral pressure pulse and, hence, to determine whether both volume and pressure pulse waveforms are influenced by the same mechanism. The digital volume pulse was recorded by photoplethysmography in 60 subjects (10 women, aged 24 to 80 years), including 20 subjects with previously diagnosed hypertension. Simultaneous recordings of the peripheral radial pulse and digital artery pulse were obtained by applanation tonometry and a servocontrolled pressure cuff (Finapres), respectively. In 20 normotensive subjects, measurements were obtained after the administration of nitroglycerin (NTG, 500 microgram sublingually). Transfer functions obtained by Fourier analysis of the waveforms were similar in normotensive and hypertensive subjects. In normotensive subjects, transfer functions were similar before and after NTG. By use of a single generalized transfer function for all subjects, the radial and digital artery pressure waveforms could be predicted from the volume pulse with an average root mean square error of 4.4+/-2.0 and 4.3+/-1.9 mm Hg (mean+/-SD) for radial and digital artery waveforms, respectively, similar to the error between the 2 pressure waveforms (4.4+/-1.4 mm Hg). The peripheral pressure pulse is related to the digital volume pulse by a transfer function, which is not influenced by effects of hypertension or NTG. Effects of NTG on the volume pulse and pressure pulse are likely to be determined by a similar mechanism.
Adult↗
Ex vivo transfection of transforming growth factor-beta1 gene to pulmonary artery segments in lung grafts.
OBJECTIVE: Proximal pulmonary artery segment transfection may provide beneficial downstream effects on the whole-lung graft. In this study, transforming growth factor-beta1 was transfected to proximal pulmonary artery segments, and the efficacy of transforming growth factor-beta1 transfection was examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation. METHODS: In the ischemia-reperfusion injury model, orthotopic left lung transplantation was performed in F344 rats. In group I, the PPAS was isolated and injected with saline solution. In 2 other groups, lipid67:DOPE:sense (group II) or antisense transforming growth factor-beta1pDNA construct (group III) was injected instead of saline solution. After cold preservation at 4 degrees C for 18 hours, lung grafts were implanted. Graft function was assessed 24 hours later. In the acute rejection model, donor lung grafts were harvested. Proximal pulmonary artery segments were injected with saline solution (group I) or sense (group II) or antisense lipid gene construct (group III) and then implanted. Graft function was assessed on postoperative day 5. RESULTS: In the ischemia-reperfusion injury study, there were no significant differences in oxygenation, wet-to-dry weight ratios, graft myeloperoxidase activity, or transforming growth factor-beta1 levels in platelet-poor serum or proximal pulmonary artery segment homogenates. In the acute rejection study, oxygenation was significantly improved in group II receiving transforming growth factor-beta1 (group II vs I and III, 136.0 +/- 32.5 vs 54.0 +/- 9.6 mm Hg and 53.8 +/- 14.8 mm Hg; P =.016 and.016). There were no significant pathologic differences. Transforming growth factor-beta1 concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls. CONCLUSIONS: Ex vivo transfection of transforming growth factor-beta1 to proximal pulmonary artery segments did not affect reperfusion injury of lung isografts. In acute rejection, however, ex vivo transfection of transforming growth factor-beta 1 to proximal pulmonary artery segments improved allograft function. This suggests that transfection to proximal pulmonary artery segments exerts beneficial downstream effects on the whole-lung allograft.
Acute Disease↗
Photoplethysmographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus.
OBJECTIVES: We sought to determine whether a simple index of pressure wave reflection may be derived from the digital volume pulse (DVP) and used to examine endothelium-dependent vasodilation in patients with type II diabetes mellitus. BACKGROUND: The DVP exhibits a characteristic notch or inflection point that can be expressed as percent maximal DVP amplitude (IP(DVP)). Nitrates lower IP(DVP), possibly by reducing pressure wave reflection. Response of IP(DVP) to endothelium-dependent vasodilators may provide a measure of endothelial function. METHODS: The DVP was recorded by photoplethysmography. Albuterol (salbutamol) and glyceryl trinitrate (GTN) were administered locally by brachial artery infusion or systemically. Aortic pulse wave transit time from the root of the subclavian artery to aortic bifurcation (T(Ao)) was measured by simultaneous Doppler velocimetry. RESULTS: Brachial artery infusion of drugs producing a greater than threefold increase in forearm blood flow within the infused limb was without effect on IP(DVP), whereas systemic administration of albuterol and GTN produced dose-dependent reductions in IP(DVP). The time between the first and second peak of the DVP correlated with T(Ao) (r = 0.75, n = 20, p < 0.0001). The effects of albuterol but not GTN on IP(DVP) were attenuated by N(G)-monomethyl-L-arginine. The IP(DVP) response to albuterol (400 microg by inhalation) was blunted in patients with type II diabetes mellitus as compared with control subjects (fall 5.9 +/- 1.8% vs. 11.8 +/- 1.8%, n = 20, p < 0.02), but that to GTN (500 microg sublingually) was preserved (fall 18.3 +/- 1.2% vs. 18.6 +/- 1.9%, p = 0.88). CONCLUSIONS: The IP(DVP) is influenced by pressure wave reflection. The effects of albuterol on IP(DVP) are mediated in part through the nitric oxide pathway and are impaired in patients with type II diabetes.
Adrenergic beta-2 Receptor Agonists↗
Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings.
Low density lipoprotein (LDL) inhibits endothelium-dependent relaxation. The mechanism is uncertain, but increased production of superoxide anion O2- with inactivation of endothelium-derived NO and formation of toxic free radical species have been implicated. We investigated effects of the cell permeable superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), the free radical scavenger vitamin C and arginine (which may reduce O2- formation) on acute LDL-induced endothelial dysfunction in rabbit aortic rings, using LDL prepared by ultracentrifugation of plasma from healthy men and aortic rings from New Zealand white rabbits. LDL (150 microg protein ml(-1) for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution at 37 degrees C and pre-constricted to 80% maximum tension with noradrenaline) to acetylcholine 82+/-10% (mean percentage difference between sum of relaxations after each concentration of acetylcholine in the presence and absence of LDL, +/-s.e.mean, n=26, P<0.001) but not to the endothelium-independent agonist nitroprusside. MnTMPyP (10 microM) reduced inhibitory effects of LDL from 124+/-27 to 56+/-17% (n=6, P<0.05). Vitamin C (1 mM) reduced inhibitory effects of LDL from 59+/-8 to 22+/-5% (n=6, P<0.05). Inhibitory effects of LDL were similar in the absence or presence of arginine (84+/-12 vs 79+/-16%, n=14, P=0.55). Effects of L-arginine (10 mM) did not differ significantly from those of D-arginine (10 mM). Acute (20 min) exposure of aortic rings to LDL impairs endothelium-dependent relaxation which can be partially restored by MnTMPyP and vitamin C. This is consistent with LDL causing increased O2- generation.
Acetylcholine↗
Activation of nitric oxide synthase by beta 2-adrenoceptors in human umbilical vein endothelium in vitro.
1. Some animal studies suggest that beta-adrenoceptor-mediated vasorelaxation is in part mediated through nitric oxide (NO) release. Furthermore, in humans, we have recently shown that forearm blood flow is increased by infusion of beta2-adrenergic agonists into the brachial artery, and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) inhibits this response. 2. The purpose of the present study was to determine whether stimulation of human umbilical vein endothelial beta-adrenoceptors causes vasorelaxation and nitric oxide generation, and whether this might be mediated by cyclic adenosine-3',5'-monophosphate (cyclic AMP). 3. Vasorelaxant responses were determined in umbilical vein rings to the nonselective beta-adrenergic agonist isoprenaline and to the cyclic AMP analogue dibutyryl cyclic AMP, following precontraction with prostaglandin F2alpha. 4. NOS activity was measured in cultured human umbilical vein endothelial cells (HUVEC) by the conversion of [3H]-L-arginine to [3H]-L-citrulline, and adenylyl cyclase activity by the conversion of [alpha-32P]-ATP to [32P]-cyclic AMP. 5. Isoprenaline relaxed umbilical vein rings, and this vasorelaxation was abolished by beta2- (but not beta1-) adrenergic blockage, and by endothelium removal or 1 mM L-NMMA. In addition, vasorelaxant responses to dibutyryl cyclic AMP were inhibited by 1 mM L-NMMA, with a reduction in Emax from 90.0+/-9.3% to 50.5+/-9.9% (P<0.05). 6. Isoprenaline 1 microM increased NOS activity in HUVEC (34.0+/-5.9% above basal, P<0.001). Furthermore, isoprenaline increased adenylyl cyclase activity in a concentration-dependent manner; this response was inhibited by beta2 (but not beta1-) adrenergic blockade. Forskolin 1 microM and dibutyryl cyclic AMP 1 mM each increased NOS activity in HUVEC, to a degree similar to isoprenaline 1 microM. The increase in L-arginine to L-citrulline conversion observed with each agent was abolished by coincubation with NOS inhibitors. 7. These results indicate that endothelial beta2-adrenergic stimulation and cyclic AMP elevation activate the L-arginine/NO system, and give rise to vasorelaxation, in human umbilical vein.
Adenylyl Cyclase Inhibitors↗
The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension.
AIMS: Brachial artery administration of nebivolol increases forearm blood flow in normotensive subjects through activation of the L-arginine/NO pathway. The aim of the present study was to investigate the effect of brachial artery administration of nebivolol in subjects with essential hypertension. METHODS: We studied eight patients with uncomplicated essential hypertension and serum cholesterol less than 6.9 mmol l-1. Antihypertensive medication was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to establish baseline blood flow, followed by increasing doses of nebivolol (88.5, 177 and 354 microg min-1, each dose for 6 min), followed by saline for 12 min, followed by a 30 min infusion of L-NMMA (2 mg min-1 ). During the final 18 min of the L-NMMA infusion, nebivolol was coinfused using the same doses as before. Forearm blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Blood flow in the noninfused arm did not change significantly throughout the study. In the infused arm blood flow increased significantly in a dose-related manner during the first series of nebivolol infusions from 2.76+/-0.39 ml min-1-1 100 ml forearm-1 during the baseline period to 4.40+/-0.60 ml min-1-1 100 ml forearm-1 (mean+/-s.e. mean, n=8, P=0.0003 by anova ). L-NMMA antagonized the vasodilator effect of nebivolol: baseline blood flow in the infused arm was 2.41+/-0.53 ml min-1 100 ml forearm-1 and 2.94+/-0.42 ml min-1 100 ml forearm-1 during coinfusion of the top dose of nebivolol with L-NMMA (P=0.0006 for an effect of L-NMMA on nebivolol response). There were no serious adverse events. CONCLUSIONS: Nebivolol causes vasodilation in the forearm vascular bed in subjects with essential hypertension. Since this response is antagonized by L-NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.
Adolescent↗
Platelet glycoprotein IIb/IIIa blockade with tirofiban: effect on aggregation caused by P256, an antibody to human IIb/IIIa receptors.
AIMS: P256 is a divalent antibody which aggregates human platelets by interaction with glycoprotein (GP) IIb/IIIa receptors. We investigated the effect of tirofiban, an antagonist of the GP IIb/IIIa receptor, on P256-mediated platelet aggregation. METHODS: Responses to agonists were measured turbidometrically at 37 degrees C in stirred citrated platelet-rich plasma from venous blood samples from healthy human volunteers. Inhibitory effects were determined by comparison with aggregation to the same concentration of agonist in a vehicle treated sample. RESULTS: Tirofiban inhibited a near maximally effective dose of P256 (10-7 mol l-1 ) with an IC50 of 9. 3x10-8 mol l-1. Tirofiban (10-7 mol l-1 ) inhibited responses to arachidonic acid, U46619 and P256 similarly, whereas aspirin (1. 1x10-4 mol l-1 ) inhibited arachidonic acid more effectively than P256 (P<0.007 by anova ). CONCLUSIONS: Tirofiban potently and selectively inhibits P256-stimulated aggregation of human platelets.
Abciximab↗
LDL particle size: an important drug target?
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Arteriosclerosis↗
Forearm vasoconstriction in response to noradrenaline and NG-monomethyl-L-arginine in essential hypertension.
A role for abnormal NO production in essential hypertension remains controversial. Blunted vasoconstriction of forearm resistance vasculature in response to N(G)-monomethyl-L-arginine (L-NMMA; an inhibitor of NO biosynthesis), relative to the response to noradrenaline, has been reported in hypertensive patients and interpreted as evidence of reduced basal NO biosynthesis. We sought to determine whether reduced sensitivity of forearm vasculature to the vasoconstrictor action of L-NMMA relative to that of noradrenaline is a consistent finding in essential hypertension. We studied a group of patients (n=32; blood pressure 176+/-4/102+/-2 mmHg; means+/-S.E.M.) and a group of healthy normotensive controls (n=32; blood pressure 130+/-2/75+/-1 mmHg). Noradrenaline (60-240 pmol.min(-1)) and L-NMMA (1-4 micromol.min(-1)) were infused into the brachial artery, and forearm blood flow was measured by venous occlusion plethysmography. The effects of each vasoconstrictor were similar in hypertensive and control subjects. The highest dose of L-NMMA reduced forearm blood flow by 0.75+/-0.12 ml.min(-1).dl(-1) in the control group and by 0.89+/-0.10 ml.min(-1).dl(-1) in the hypertensive group. The study had 90% power (with P=0.05) to detect a 10% difference in forearm blood flow response between the hypertensive and control groups. We conclude that reduced sensitivity of forearm resistance vasculature to the vasoconstrictor action of L-NMMA is not a universal feature of essential hypertension. This argues against a primary role for reduced basal NO biosynthesis in skeletal muscle resistance vessels in the pathogenesis of essential hypertension.
Adult↗
Lack of effect of vitamin E on L-arginine-responsive endothelial dysfunction in patients with mild hypercholesterolaemia and coronary artery disease.
1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits. We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group. Lipid profiles remained similar before and after supplementation in both groups. Forearm blood flow responses to acetylcholine (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were similar before and after supplementation in both groups. Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 micrograms/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.
Acetylcholine↗
Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise.
OBJECTIVE: To compare effects of N(G)-monomethyl-L-arginine (L-NMMA; a NO synthase inhibitor) and L-arginine (a NO synthase substrate) on haemodynamics in healthy men at rest and during exercise. METHODS: We infused L-NMMA and saline placebo intravenously in two groups of eight healthy men. Each group underwent a two-phase, randomized, single-blind crossover study. Men in one group received 3 mg/kg L-NMMA and men in the other group received 6 mg/kg L-NMMA. Haemodynamic measurements were performed before, during and after a 12 min stepped exercise protocol starting 6 min after the intravenous infusion. A further six men received, according to the same study design, 30 g L-arginine over 30 min and saline placebo before exercise. Blood pressure was measured by sphygmomanometry and cardiac output by bioimpedance, allowing computation of total systemic vascular resistance index (SVRI). RESULTS: Infusion of 6 mg/kg L-NMMA into men at rest produced modest increases (compared with effect of saline placebo) in systolic and diastolic blood pressures of 4.1 +/- 1.1 and 12.6 +/- 3.5%, respectively (means +/- SEM, P < 0.01 for both comparisons) and a marked increase in SVRI of 39.2 +/- 5.2% (P < 0.01). Cardiac index and heart rate were 22.0 +/- 3.3 and 17.0 +/- 4.4% lower after administration of L-NMMA (P < 0.01 for each comparison) than after infusion of saline placebo. During exercise there was no significant difference between total SVRI after infusions of L-NMMA and saline (difference not significant, diminished with increasing exercise). Six minutes into recovery the difference between total SVRI after infusions of L-NMMA and saline reappeared with SVRI 25 +/- 6.9% higher after infusion of L-NMMA than after infusion of saline (P < 0.01). Administration of L-arginine had no significant effect on haemodynamics in men at rest, during exercise and during recovery. CONCLUSIONS: Effects of L-NMMA on total systemic vascular resistance during exercise are less marked than are those on subjects at rest, probably because vasodilatation of resistance vessels of skeletal muscle during exercise is mediated mainly by factors other than NO. Our results also suggest that NO synthesis in healthy men is not substrate limited either at rest or during exercise.
Adult↗
Evidence for a difference in nitric oxide biosynthesis between healthy women and men.
There is indirect evidence for a gender difference in nitric oxide (NO) synthesis from vascular endothelium. The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-[15N]2-guanidino arginine. Twenty-four healthy volunteers (13 men aged 22 to 40 years and 11 women aged 23 to 42 years) participated in this study. No subjects were receiving any medication. Women were studied between the 7th and 14th days of their menstrual cycles. Arterial blood pressure was measured oscillometrically, and 1.13 micromol L-[15N]2 arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours in separate 12-hour periods. Urinary 15N/14N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. Mean 36-hour urinary 15N nitrate excretion was greater in women than in men (2111+/-139 versus 1682+/-87 etamol; P<0.05). Furthermore, total urinary 15N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects (coefficient of correlation, 0.47; P=0.022). The present data show that whole-body production of NO is greater in healthy premenopausal women than in men under ambulatory conditions. The cellular origin of NO measured in this study is unknown, but differences in endothelial production could underlie differences in vascular function between men and women.
Adult↗
When it's not a rheumatic disease.
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Cardiovascular Diseases↗
Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by beta-adrenergic agonists in human forearm.
BACKGROUND: We examined whether vasodilator responses to beta-agonists in human forearm vasculature are mediated in part through the nitric oxide pathway. METHODS AND RESULTS: We measured forearm blood flow responses to brachial artery infusions of beta-adrenergic agonists in healthy men. Salbutamol was more than 100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5 nmol.min-1) did not cause tachyphylaxis to an identical repeated infusion after a 24-minute recovery period. Vasodilators were infused with this sequence during coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 mumol.min-1), an inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol.min-1) by 59 +/- 7% (n = 5) and inhibited those to salbutamol (0.3 to 3.5 nmol.min-1) by 52 +/- 6% (n = 8). L-NMMA had no significant effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol.min-1, n = 8), verapamil (20 to 80 nmol.min-1, n = 8), or prostacyclin (0.08 to 0.24 nmol.min-1, n = 8). CONCLUSIONS: These results suggest that beta-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta 2-adrenergic receptors and are dependent on nitric oxide synthesis.
Adolescent↗
Preserved endothelial function in patients with severe hypertriglyceridemia and low functional lipoprotein lipase activity.
OBJECTIVES: We sought to determine whether hypertriglyceridemia in patients with lipoprotein lipase (LPL) dysfunction is associated with endothelial dysfunction in resistance vessels of the forearm vasculature. BACKGROUND: Vasodilator responses to acetylcholine, acting through stimulation of nitric oxide (NO) release from the endothelium, are impaired in hypercholesterolemia and normalized by L-arginine, suggesting dysfunction of the L-arginine/NO pathway. Similar abnormalities have been reported in conditions associated with hypertriglyceridemia, such as non-insulin-dependent diabetes. The relation between endothelial function and plasma triglyceride concentrations has, however, not previously been studied in vivo. METHODS: We examined forearm blood flow responses to brachial artery infusions of acetylcholine (alone and with L-arginine) and nitroprusside (an NO donor) in 17 patients with severe hypertriglyceridemia (mean [+/- SD] plasma triglyceride concentration 1,914 +/- 1,288 mg/dl) but normal low density lipoprotein cholesterol (89 +/- 31 mg/dl) and in 34 normolipidemic control subjects. Severe LPL dysfunction was demonstrated in 10 of 17 patients. RESULTS: Acetylcholine (7.5 and 15 microg/min) produced similar forearm blood flow responses in hypertriglyceridemic patients (mean [+/- SEM] 7.7 +/- 0.9 and 10.5 +/- 1.2 ml/min per 100 ml) and in control subjects (7.5 +/- 0.6 and 11.0 +/- 0.8 ml/min per 100 ml, p = 0.78 by analysis of variance). Responses to acetylcholine co-infused with L-arginine (10 mg/min) and nitroprusside (3 and 10 microg/min) were also similar in hypertriglyceridemic patients and control subjects (p = 0.93 and p = 0.27 for acetylcholine with L-arginine and nitroprusside, respectively). The ratio response to acetylcholine/response to nitroprusside differed between hypertriglyceridemic patients and control subjects by only 1%. The study had >90% power (alpha = 0.05) to detect a difference >30% in this ratio. CONCLUSIONS: Severe hypertriglyceridemia associated with LPL dysfunction is not associated with the degree of endothelial dysfunction seen in moderate hypercholesterolemia when responses to acetylcholine are impaired by >40%.
Acetylcholine↗
Vasoconstrictor sensitivity to noradrenaline and NG-monomethyl-L-arginine in men and women.
1. Nitric oxide has potential anti-atherogenic actions as well as regulating vascular tone. Animal studies suggest that there are sex differences in basal nitric oxide biosynthesis, but it is not known whether such differences exist between men and women. 2. We have investigated this question by measuring forearm blood flow responses, using venous occlusion plethysmography, to brachial artery infusion of NG-monomethyl-L-arginine (an inhibitor of NO biosynthesis) and noradrenaline in 40 healthy subjects (20 men and 20 premenopausal women). Mean arterial blood pressure was 89 +/- 10 mmHg (mean +/- SD) in men and 87 +/- 9 mmHg in women, and mean total cholesterol was 4.25 +/- 0.99 mmol/l (mean +/- SD) and 4.26 +/- 0.80 mmol/l respectively. 3. In men, vasoconstrictor responses to NG-monomethyl-L-arginine, 1-4 mumol/min (15-28% mean reduction in blood flow), were consistently less than responses to noradrenaline, 60-240 pmol/min (26-37%), whereas in women, vasoconstrictor responses to NG-monomethyl-L-arginine (19-30%) were consistently greater than those to noradrenaline (11-17%). The sex difference in relative sensitivity to vasoconstrictors was significant (P < 0.001). 4. Our findings are consistent with either greater sensitivity to noradrenaline in men compared with premenopausal women, or a greater basal nitric oxide biosynthesis in premenopausal women compared with men.
Adult↗
Influence of sex on sodium-proton exchange-dependent swelling of platelets from patients with essential hypertension.
OBJECTIVE: To determine whether sex influences the rate of sodium-proton (Na+-H+)-exchange-dependent swelling of platelets from patients with essential hypertension and normotensive controls. METHOD: Platelet swelling was detected by measuring the change in optical density of platelet suspensions added to sodium propionate buffer, pH 6.7, at 37 degrees C. We studied 56 subjects, 28 men and 28 women, each group containing 14 normotensive and 14 hypertensive subjects. The groups were well matched for sex, ethnicity and age. RESULTS: That platelet swelling was dependent on Na+-H+ exchange was demonstrated by performing blockade by 5-(N,N-hexamethylene)-amiloride and by measuring its dependence on extracellular Na+ concentration. The rate of swelling of platelets from hypertensive men [(14.2 +/- 0.9) x 10(-3)/s] was higher than that of those from normotensive men [(10.1 +/- 0.5) x 10(-3)/s], normotensive women [(10.0 +/- 0.5) x 10(-3)/s] and hypertensive [(11.1 +/- 0.8) x 10(-3)/s] women. The interaction between sex and hypertension was significant (P < 0.05 by analysis of variance). CONCLUSIONS: Sex influences the effect of hypertension on the rate of swelling of platelets exposed to sodium propionate (pH 6.7).
Adult↗