GENDER DIFFERENCES IN THE RENAL NITRIC-OXIDE (NO) SYSTEM - DISSOCIATION BETWEEN EXPRESSION OF ENDOTHELIAL NO SYNTHASE AND RENAL HEMODYNAMIC-RESPONSE TO NO SYNTHASE INHIBITION

Many studies have shown that nitric oxide (NO) production is higher in the systemic vasculature of females than males and is stimulated duri ng pregnancy, a high estrogen state. The present study was performed i n rats to determine whether females had a greater expression of endoth elial NO synthase (eNOS) in kidneys than did males; whether there were gender differences in the excretion of NO metabolites, nitrate/nitrit e; and whether there were gender differences in the renal hemodynamic response to NO synthase inhibition. The renal levels of eNOS mRNA (as measured by ribonuclease protection assays) and protein (as measured b y Western blot) were 80% higher in kidneys from females than from male s (P < .001). Urinary excretion of NO metabolites, nitrate/nitrite, we re not different between males and females. To inhibit eNOS, rats were treated with nitro-L-arginine methyl ester (L-NAME, 3 to 4 mg/kg/day) for 2 weeks. Although there were no differences in basal renal hemody namics between males and females, when factored for kidney weight, chr onic L-NAME increased renal vascular resistance by 130% in males but b y only 60% in females, and decreased renal plasma flow by 40% in males but had no effect in females. These data show that although the renal levels of eNOS mRNA and protein are higher in females than in males, the renal vasculature of males is more responsive to NO synthase inhib ition. The data suggest that the renal vasculature of males may be mor e dependent on NO than is the renal vasculature in females. (C) 1998 A merican Journal of Hypertension, Ltd.