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.

Abstract-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 15 N nitrate excreted in urine after the intravenous administration of L-[ 15 N] 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 mol L-[ 15 N] 2 arginine was administered intravenously after an overnight fast. Urine was collected for the next 36 hours in separate 12-hour periods. Urinary 15 N/ 14 N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. Mean 36-hour urinary 15 N nitrate excretion was greater in women than in men (2111Ϯ139 versus 1682Ϯ87 mol; PϽ0.05). Furthermore, total urinary 15 N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects (coefficient of correlation, 0.47; Pϭ0.022). 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. (Hypertension. 1998;32:730-734.) Key Words: endothelium-derived relaxing factor Ⅲ arginine Ⅲ nitrates Ⅲ gender Ⅲ adults P remenopausal women have less atheromatous arterial disease, including stroke or coronary artery disease, than men of similar age.1 Synthesis of nitric oxide (NO) by the endothelium regulates vascular tone in the arterial bed and modulates interactions between the endothelium and circulating blood cells, including platelets and leukocytes.2 Previous studies have suggested that a gender difference in the production of NO due to ovarian hormones (ie, estrogens) could contribute to this low risk of cardiovascular events in women of reproductive age. However, the role of NO is controversial because increased 3,4 or diminished 5,6 production in women compared with men has been reported. It is possible that the indirect nature and relative specificity of the methods used for the measurement of NO in those studies might account for these discrepancies. Measurement of urinary or serum nitrate is highly affected by diet.7 Cyclic GMP is also the second messenger of atrial natriuretic peptide, 8 and exhaled NO reflects local biosynthesis in the lung and/or upper airways rather than in the whole body. We have developed a sensitive and specific method to measure more directly the conversion of L-arginine to NO. 9 The method is based on the measurement of 15 N nitrate (stable oxidation product of NO) excretion in urine after intravenous single administration of the stable isotope L-[ 15 N] 2 -guanidino arginine. Us...

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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.