Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats

Huang, Bing; Cheung, Warren J.; Wang, Hao; Tan, Junhui; White, Roselyn; Leenen, Frans H. H.

doi:10.1152/ajpheart.00024.2006

Cited by 52 publications

(68 citation statements)

References 43 publications

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“…This pressor effect was partially blocked by the MR blocker eplerenone in SHRSPs, indicating that the effect of Na + might be mediated by MR activation. ICV infusion of the MR blockers, spironolactone 46 or benzamil, 47 prevented Na + -induced sympathoexcitatory and pressor responses in WKY rats. It has also been reported that ICV infusion of eplerenone attenuated ENaC expression in mice with pressure overload.…”

Section: Discussionmentioning

confidence: 91%

Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

et al. 2012

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Mineralocorticoid receptor (MR) is recognized as a target for therapeutic intervention in hypertension and heart failure. MRs in the central nervous system are thought to have an important role in blood pressure regulation. Thus, we examined whether activation of the MR pathway in the rostral ventrolateral medulla (RVLM) of the brainstem contributes to the neural mechanism of hypertension in stroke-prone spontaneously hypertensive rats (SHRSPs). We microinjected eplerenone, aldosterone or Na + -rich artificial cerebrospinal fluid (aCSF) into the RVLM of anesthetized Wistar-Kyoto (WKY) rats and SHRSPs. Arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. The expressions of the MR protein and the serumand glucocorticoid-regulated kinase protein (Sgk1), which is a marker of MR activity, in the RVLM were measured by western blot analysis. Bilateral microinjection of eplerenone into the RVLM decreased AP and RSNA in WKY rats and SHRSPs, and the decreases in those variables were significantly greater in SHRSPs than WKY rats. Microinjection of aldosterone or Na + -rich aCSF into the RVLM increased AP and RSNA dose-dependently. The increases in those variables were significantly greater in SHRSPs than in WKY rats. The pressor responses of aldosterone or Na + -rich aCSF were attenuated by the prior injection of eplerenone in SHRSPs. Sgk1 expression levels in the RVLM were significantly greater in SHRSPs than in WKY rats. These findings suggest that activation of MRs in the RVLM enhances sympathetic activity, thereby contributing to the neural mechanism of hypertension in the SHRSP.

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Section: Discussionmentioning

confidence: 91%

Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

et al. 2012

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“…Plasma and brain aldosterone were measured by RIA as described previously (18). Briefly, plasma was applied to preconditioned C18 cartridges, the cartridges were washed with 12% methanol, and aldosterone was eluted with 80% methanol.…”

Section: Experimental Protocolmentioning

confidence: 99%

Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

Huang¹,

White²,

Jeng³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na ϩ ] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by ϳ35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by ϳ65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na ϩ ]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.brain; corticosterone; high-salt diet IN DAHL SALT-SENSITIVE (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na ϩ concentration ([Na ϩ ]) and causes sympathetic hyperactivity and hypertension (19). Saltinduced sympathetic hyperactivity and hypertension can be prevented by central blockade of steroid biosynthesis by the steroid synthase 3␤-hydroxysteroid dehydrogenase (HSD) inhibitor trilostane (14) or central blockade of mineralocorticoid receptors (MR) (13).The agonist binding to the MR in the central nervous system (CNS) has not been defined, nor has its origin, i.e., whether it is derived from the circulation or locally produced, been determined. Inasmuch as central infusion of trilostane has antihypertensive effects (14), it appears that local production of a steroid in the CNS plays a major role. However, trilostane blocks the synthesis not only of the mineralocorticoid hormone aldosterone but also of the glucocorticoid hormone corticosterone (14, 24). Aldosterone and corticosterone can be synthesized in the brain (11,12,24). Aldosterone and corticosterone bind MR with equal affinity (3), but the presence of the corticosterone-inactivating enzyme 11␤-HSD-2 enhances aldosterone selectivity of the MR in brain regions where it is expressed, such as the paraventricular nucleus of the hypothalamus (34).There is no evidence that, in Dahl S rats, high salt intake actually increases aldosterone or corticosterone production and release in brain regions implicated in sympathetic regulation or, alternatively, causes changes in MR or 11␤-HSD-2 expression. FAD286 is a specific aldosterone synthase (CYP11B2) blocker that appears to have no effects on corticosterone synthesis (25). Oral administration...

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“…Intracerebroventricular infusion of Fab fragments that specifically bind ouabain-like compounds ("ouabain") (31) blocks these responses, whereas intracerebroventricular infusion of spironolactone or benzamil inhibits increases in brain "ouabain" and hypertension in response to chronic intracerebroventricular infusion of Na ϩ -rich aCSF (12,36,37). These findings suggest that mineralocorticoid receptors (MRs) and benzamil-blockable Na ϩ channels or transporters in the CNS mediate the release of "ouabain" and hypertension caused by a chronic increase in CSF [Na ϩ ].…”

mentioning

confidence: 99%

Mechanisms in the PVN mediating local and central sodium-induced hypertension in Wistar rats

Gabor

Leenen²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats

Cited by 52 publications

References 43 publications

Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

Mechanisms in the PVN mediating local and central sodium-induced hypertension in Wistar rats

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