Stimulation of beta2-adrenergic receptors causes greater forearm vasodilation in premenopausal women, at midmenstrual cycle, than it does in men. This is sufficient to explain why vasoconstriction to brachial artery norepinephrine is attenuated in such women.

Exercise markedly influences pulse wave morphology, but the mechanism is unknown. We investigated whether effects of exercise on the arterial pulse result from alterations in stroke volume or pulse wave velocity (PWV)/large artery stiffness or reduction of pressure wave reflection. Healthy subjects (n = 25) performed bicycle ergometry. with workload increasing from 25 to 150 W for 12 min. Digital arterial pressure waveforms were recorded using a servo-controlled finger cuff. Radial arterial pressure waveforms and carotid-femoral PWV were determined by applanation tonometry. Stroke volume was measured by echocardiography, and brachial and femoral artery blood flows and diameters were measured by ultrasound. Digital waveforms were recorded continuously. Other measurements were made before and after exercise. Exercise markedly reduced late systolic and diastolic augmentation of the peripheral pressure pulse. At 15 min into recovery, stroke volume and PWV were similar to baseline values, but changes in pulse wave morphology persisted. Late systolic augmentation index (radial pulse) was reduced from 54 +/- 3.9% at baseline to 42 +/- 3.7% (P < 0.01), and diastolic augmentation index (radial pulse) was reduced from 37 +/- 1.8% to 25 +/- 2.9% (P < 0.001). These changes were accompanied by an increase in femoral blood flow (from 409 +/- 44 to 773 +/- 48 ml/min, P < 0.05) and an increase in femoral artery diameter (from 8.2 +/- 0.4 to 8.6 +/- 0.4 mm, P < 0.05). In conclusion, exercise dilates muscular arteries and reduces arterial pressure augmentation, an effect that will enhance ventricular-vascular coupling and reduce load on the left ventricle.

Background-Nitric oxide (NO) has a pivotal role in the regulation of vascular tone and blood flow, with dysfunctional release contributing to disease pathophysiology. These effects have been attributed to NO production by the endothelial NO synthase (eNOS); however, recent evidence suggests that a neuronal NO synthase (nNOS) may also be expressed in arterial vessels. Methods and Results-We undertook a first-in-humans investigation of the role of nNOS in the local regulation of vascular blood flow in healthy subjects. Brachial artery infusion of the nNOS-specific inhibitor S-methyl-L-thiocitrulline (SMTC, 0.025 mol/min to 0.2 mol/min) caused a dose-dependent reduction in basal flow, with a 30.1Ϯ3.8% decrease at the highest dose (nϭ10; meanϮSE; PϽ0.01). The effect of SMTC was abolished by coinfusion of the NO synthase substrate L-arginine but was unaffected by D-arginine. A similar reduction in basal flow with the nonselective NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA; 37.4Ϯ3.1%, nϭ10) required a 20-fold higher dose of 4 mol/min. At doses that produced comparable reductions in basal flow, only L-NMMA (4 mol/min) and not SMTC (0.2 mol/min) inhibited acetylcholine-induced vasodilation; however, both SMTC and L-NMMA inhibited the forearm vasodilator response to mental stress. Conclusions-Basal forearm blood flow in humans is regulated by nNOS-derived NO, in contrast to the acetylcholinestimulated increase in blood flow, which, as shown previously, is mediated primarily by eNOS. These data indicate that vascular nNOS has a distinct local role in the physiological regulation of human microvascular tone in vivo. Key Words: nitric oxide synthase Ⅲ blood flow Ⅲ vasculature Ⅲ nitric oxide Ⅲ endothelium Ⅲ vasodilation N itric oxide (NO) has a pivotal role in the regulation of vascular tone and blood flow through its potent vasodilator activity. 1 It is well established that local intra-arterial infusion of the nonselective NO synthase (NOS) inhibitor N G -monomethyl-L-arginine (L-NMMA) into the human forearm significantly reduces resting blood flow, 2 whereas systemic L-NMMA infusion causes a transient increase in blood pressure. 3 Similar effects are described in animals, including mice lacking the endothelial NOS (eNOS) isoform, 4 and have generally been attributed to the continuous release of NO from eNOS expressed in the vascular endothelium. The NO-dependent vasodilator effects elicited by increases in flow or by acetylcholine infusion are also thought to involve endothelial eNOS, 1 and impairment of these responses (known as "endothelial dysfunction") is a recognized prognostic marker for future cardiovascular events. 5,6 Interestingly, the impaired flow-or acetylcholine-mediated vasodilation observed in human cardiovascular disease does not always correlate well with basal NO release, 7 which suggests that regulation of vascular function by NO may be subserved by different mechanisms and possibly different sources of NO. Indeed, recent experimental studies have suggested that neuronal NOS (nNOS)-derive...

Background-Metabolic factors, including plasma concentrations of cholesterol and insulin resistance, may influence blood pressure through effects on vascular reactivity. Such effects might influence blood pressure during exercise more strongly than at rest. Methods and Results-We examined whether there is an association between serum cholesterol or insulin resistance and change in blood pressure during mild exercise. Blood pressure was measured at rest and during fixed low-workload bicycle ergometry (50, 75, and 100 W, each for 3 minutes) in 75 healthy active men (age, 18 to 66 years). Blood pressure at rest was not significantly correlated with serum cholesterol or insulin resistance (estimated from the fasting glucose-insulin product). The change from resting values in diastolic but not systolic blood pressure during exercise was correlated with serum cholesterol (RϾ0.47, PϽ0.0001 for each workload) and insulin resistance (RϾ0.38, PϽ0.01 for each workload). Serum cholesterol and insulin resistance were the only independent predictors of the change in diastolic blood pressure during exercise in a stepwise regression model incorporating age, body mass index, serum cholesterol, triglycerides, HDL cholesterol, insulin resistance, and heart rate during exercise. In a further study, the change in diastolic blood pressure during exercise was greater in men with uncomplicated type 2 diabetes (13.