The primary objective of this clinical research program is to assess the importance of vascular nitric oxide (NO) production in the regulation of cardiovascular responses to stress (reactivity), with special attention given to NO effects on gender and racial differences in reactivity. NO plays an important role in blood pressure (BP) regulation, and potentially influences the development of hypertension. Studies by ourselves and others indicate that BP reactivity is strongly inversely related to NO production during stress. However, the contribution of NO in the regulation of reactivity has not been fully explored in human studies. In particular, estrogen-induced endothelial NO production may contribute to differences in reactivity between men and premenopausal women, and there may be differences in NO production among blacks and those with a family history of hypertension (FH) that may affect reactivity. Our preliminary studies support these ideas. In our proposed studies, normotensive subjects will be put on a low nitrate/nitrite diet for two days, and then have psychophysiologic testing with measures of BP, forearm blood flow, and plasma levels of NO metabolites (nitrates/nitrites) and catecholamines taken before and after two stressors (speech task and cold pressor). Two separate studies using the above protocol will employ a within-subjects design to determine the effects of two factors (menstrual cycle variation of estrogen and L-arginine loading to induce NO production) on the relationship of NO and reactivity. Our major hypotheses are: 1) NO production contributes significantly to the regulation of reactivity, and is inversely related to reactivity measures, particularly those related to vasoconstriction; 2) Among women, higher levels of estrogen in the late luteal phase induce greater vascular NO production and lower reactivity than in the low-estrogen menstrual phase; 3) individuals at risk for hypertension (blacks, those with FH) have less NO change with stress than low risk individuals, and this difference contributes to differences in reactivity; 4) dietary supplementation with the NO precursor L-arginine increases NO production and diminishes reactivity, with the greatest effects occurring among blacks and those with FH; and 5) NO is inversely related to measures of adrenergic activity, and both systems contribute to the regulation of reactivity.
