Abstract Angiotensin II (ANG II)-induced mitogen-activated protein kinase (MAPK) signaling upregulates angiotensin II type-1 receptors (AT 1 R) in hypothalamic paraventricular nucleus (PVN) and contributes to AT 1 R-mediated sympathetic excitation in heart failure. Aldosterone has similar effects to increase AT 1 R expression in the PVN and sympathetic drive. The present study was undertaken to determine whether aldosterone also activates the sympathetic nervous system via MAPK signaling and, if so, whether its effect is independent of ANG II and AT 1 R. In anesthetized rats, a 4-h intravenous infusion of aldosterone induced increases ( P < 0.05) in phosphorylated (p-) p44/42 MAPK in PVN, PVN neuronal excitation, renal sympathetic nerve activity (RSNA), mean blood pressure (MBP), and heart rate (HR). Intracerebroventricular or bilateral PVN microinjection of the p44/42 MAPK inhibitor PD-98059 reduced the aldosterone-induced RSNA, HR, and MBP responses. Intracerebroventricular pretreatment (5 days earlier) with pooled small interfering RNAs targeting p44/42 MAPK reduced total and p-p44/42 MAPK, aldosterone-induced c-Fos expression in the PVN, and the aldosterone-induced increases in RSNA, HR, and MBP. Intracerebroventricular infusion of either the mineralocorticoid receptor antagonist RU-28318 or the AT 1 R antagonist losartan blocked aldosterone-induced phosphorylation of p44/42 MAPK and prevented the increases in RSNA, HR, and MBP. These data suggest that aldosterone-induced sympathetic excitation depends upon that AT 1 R-induced MAPK signaling in the brain. The short time course of this interaction suggests a nongenomic mechanism, perhaps via an aldosterone-induced transactivation of the AT 1 R as described in peripheral tissues. extracellular related kinase 1/2 mineralocorticoid receptor hypothalamic paraventricular nucleus blood pressure « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpheart.​00856.​2011 AJP - Heart February 2012 vol. 302 no. 3 H742-H751 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpheart.00856.2011v1 302/3/H742 most recent Classifications Cardiovascular Neurohormonal Regulation Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Zhang, Z. Articles by Felder, R. B. PubMed PubMed citation Articles by Zhang, Z. Articles by Felder, R. B. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Heart About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6135 Online ISSN: 1522-1539 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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