title: Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats.
abstract: 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 serum- and 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakagaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Matsukawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nishihara
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakano
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D000077545:Eplerenone; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008845:Microinjections; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone