Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system.

Abstract

Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40mg/kg/day po) for 6days. Renal denervation reduced MAP in old females compared to sham (172±6 vs. 193±6mm Hg; P<0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142±10 vs. 161±6mm Hg; P<0.05 vs. RD, P<0.05 vs. baseline). However, female SHR rats remained significantly hypertensive despite both pharmacological intervention and RD. The data suggest that both the renal sympathetic nervous system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women.