Sex Differences in the Abundance of Endothelial Nitric Oxide in a Model of Genetic Hypertension

Abstract

Abstract A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N G -nitro- l -arginine methyl ester to be significantly greater in WKY compared 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 significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P =.016). The EC 50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: −1.1 to −0.2; P =.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P =.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats’ carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P =.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.