SEX-DIFFERENCES IN THE ABUNDANCE OF ENDOTHELIAL NITRIC-OXIDE IN A MODEL OF GENETIC-HYPERTENSION

A deficiency of nitric oxide may be responsible for the increased vasc ular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relat ively protected from hypertension and cardiovascular complications. Le vels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability be tween stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar- Kyoto rats (WKY) and that superoxide may be responsible for at least s ome of these differences. We studied vascular reactivity in endotheliu m-intact aortic rings from WKY and SHRSP. We measured nitric oxide syn thase activity in endothelial cells removed from aortas and also measu red circulating nitrite/nitrate levels. We found the response to N-G-n itro-L-arginine methyl ester to be significantly greater in WKY compar ed with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was signific antly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016) . The EC50 for relaxation to carbachol was significantly greater in ma le rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) withi n the SHRSP strain. The maximum relaxation to carbachol was significan tly attenuated in stroke prone spontaneously hypertensive compared wit h Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbam ate had a significantly greater effect on the stroke prone spontaneous ly hypertensive rats' carbachol response than that of Wistar-Kyoto rat s (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nit ric oxide availability may be responsible for sex differences independ ently of endothelial nitric oxide synthase activity and superoxide.