Testosterone and Renal Renin Angiotensin System in salt sensitive hypertension.

Abstract

Sex hormones are important blood pressure (BP) regulators. The aim of this study was to test the hypothesis that castration attenuated salt sensitive hypertension in male Dahl (DS) and to determine if changes in Renin Angiotensin System (RAS) are involved. Intact and castrated male DS rats were placed on low sodium diet (0.3%, LS) or 4 weeks of high sodium diet (8%, HS). Mean arterial pressure (MAP) was monitored by telemetry. Kidney levels of angiotensinogen (AGTN), renin and AT-1R mRNA were measured by real time RT-PCR in LS and HS diet. Plasma renin activity (PRA) was determined by radioimmunoassay. Placement of DS rats on HS for 4 weeks caused a progressive increase in MAP in males (from 121±2 to 168±2 mm Hg; LS vs. HS; p <0.05). Castration in males attenuated hypertension (168±2 vs. 145±3 mmHg; male vs.castrate; p <0.05). Development of salt sensitive hypertension in male DS rats was associated with 3-fold increase of renal AGTN mRNA (p<0.05) and this effect was abolished by castration. Renin mRNA expression and PRA decreased with salt (40% decrease; p< 0.05) and was not affected by gonadectomy. AT-1R mRNA in kidney was not altered by either castration or salt. Our data suggest that testosterone augments the hypertensive response to HS in male DS. Intrarenal RAS may be involved in salt sensitive hypertension and testosterone could be an important modulator of this system in DS.