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 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P < 0.05). Losartan reduced MAP in both sham and RD rats similarly (numerically and by percentage) (142 ± 10 vs. 161 ± 6 mm 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.

Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men

“…After 4 weeks of testosterone supplementation in young or old males, radiotelemeters (Model: HD‐S10; DSI, Minneapolis, MN) were implanted, as we have described previously . After a 2‐week recovery period, baseline mean arterial pressure (MAP) was measured for 5 days and recorded.…”

“…Testosterone levels were measured in untreated rats at various ages (3,5,7,8,9,12,14,18, and 22 months) and in rats, aged 22 weeks or 18 to 22 months receiving testosterone pellets or controls, in serum drawn from the jugular vein with rats under isoflurane anesthetic, and using a commercially available radioimmunoassay kit (Coat-A-Count testosterone kit; Diagnostic Products Corporation, Los Angeles, CA), as we have described previously. 11 Plasma estradiol was measured at the end of the experiment by Ultrasensitive Estradiol Kit (Diagnostic Systems Laboratories, Inc, Webster, TX), according to manufacturer's recommendations, as we previously described.…”

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

“…Based on this timeline, the natural course of the SHR model can be divided into the following categories: prehypertensive (Ͻ6 wk of age), developing hypertension (7-12 wk of age), and established hypertension (Ͼ12 wk old) (71,639). The characteristics of this model resemble essential hypertension in humans, and the SHR model has been extensively used in studies involving stroke (9,256,621), myocardial hypertrophy (319,390), changes in vascular resistances (45,184,728), and hypertension and sex hormones (425,426,751,753), among many others.…”

Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

“…Alterations in the functionality of the perivascular innervation are known to play an important role in hypertension. In fact, hypertension has been reported to alter the release and/or function of neuronal NO [ 24 , 25 , 31 ], CGRP [ 26 , 35 ] and NA [ 36 – 38 ].…”