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 wa s to determine NO production more directly in healthy women and men by the measurement of N-15 nitrate excreted in urine after the intraveno us administration of L-[N-15](2)-guanidino arginine. Twenty-four healt hy volunteers (13 men aged 22 to 40 years and 11 women aged 23 to 42 y ears) participated in this study. No subjects were receiving any medic ation. Women were studied between the 7th and 14th days of their menst rual cycles. Arterial blood pressure was measured oscillometrically, a nd 1.13 mu mol L-[N-15](2) arginine was administered intravenously aft er an overnight fast. Urine was collected for the next 36 hours in sep arate 12-hour periods. Urinary N-15/N-14 nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer. Mean 36-hour ur inary N-15 nitrate excretion was greater in women than in men (2111+/- 139 versus 1682+/-87 eta mol; P<0.05). Furthermore, total urinary N-15 nitrate excretion was associated inversely with the mean arterial blo od 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 ambulat ory conditions. The cellular origin of NO measured in lis study is unk nown, but differences in endothelial production could underlie differe nces in vascular function between men and women.