HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/H1067    most recent 01131.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Zhang, Z.-H. Articles by Felder, R. B. Search for Related Content PubMed PubMed Citation Articles by Zhang, Z.-H. Articles by Felder, R. B.

Aldosterone acts centrally to increase brain renin-angiotensin system activity and oxidative stress in normal rats

¹Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa; and Department of ²Veterans Affairs Medical Center, Iowa City, Iowa

Submitted 29 September 2007 ; accepted in final form 27 December 2007

Aldosterone acts upon mineralocorticoid receptors in the brain to increase blood pressure and sympathetic nerve activity, but the mechanisms are still poorly understood. We hypothesized that aldosterone increases sympathetic nerve activity by upregulating the renin-angiotensin system (RAS) and oxidative stress in the brain, as it does in peripheral tissues. In Sprague-Dawley rats, aldosterone (Aldo) or vehicle (Veh) was infused for 1 wk via an intracerebroventricular (ICV) cannula, while RU-28318 (selective mineralocorticoid receptor antagonist), Tempol (superoxide dismutase mimetic), losartan [angiotensin II type 1 receptor (AT₁R) antagonist], or Veh was infused simultaneously via a second ICV cannula. After 1 wk of ICV Aldo, plasma norepinephrine was increased and mean arterial pressure was slightly elevated, but heart rate was unchanged. These effects were ameliorated by ICV infusion of RU-28318, Tempol or losartan. Aldo increased expression of AT₁R and angiotensin-converting enzyme (ACE) mRNA in hypothalamic tissue. RU-28318 minimized and Tempol prevented the increase in AT₁R mRNA; RU-28318 prevented the increase in ACE mRNA. Losartan had no effect on AT₁R or ACE mRNA. Immunohistochemistry revealed Aldo-induced increases in dihydroethidium staining (indicating oxidative stress) and Fra-like activity (indicating neuronal excitation) in neurons of the hypothalamic paraventricular nucleus (PVN). RU-28318 prevented the increases in superoxide and Fra-like activity in PVN; Tempol and losartan minimized these effects. Acute ICV infusions of sarthran (AT₁R antagonist) or Tempol produced greater sympathoinhibition in Aldo-treated than in Veh-treated rats. Thus aldosterone upregulates key elements of brain RAS and induces oxidative stress in the hypothalamus. Aldosterone may increase sympathetic nerve activity by these mechanisms.

mineralocorticoid receptor; central nervous system; angiotensin-converting enzyme; angiotensin II type 1 receptor; sympathetic nerve activity

This article has been cited by other articles:

				M. M. Shafiq and A. B. Miller Blocking aldosterone in heart failure Therapeutic Advances in Cardiovascular Disease, October 1, 2009; 3(5): 379 - 385. [Abstract] [PDF]

				Y. Minoura, H. Onimaru, K. Iigaya, I. Homma, and Y. Kobayashi Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R699 - R706. [Abstract] [Full Text] [PDF]

				Y.-M. Kang, Y. Ma, J.-P. Zheng, C. Elks, S. Sriramula, Z.-M. Yang, and J. Francis Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension Cardiovasc Res, June 1, 2009; 82(3): 503 - 512. [Abstract] [Full Text] [PDF]

				B. Xue, D. Badaue-Passos Jr, F. Guo, C. E. Gomez-Sanchez, M. Hay, and A. K. Johnson Sex differences and central protective effect of 17{beta}-estradiol in the development of aldosterone/NaCl-induced hypertension Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1577 - H1585. [Abstract] [Full Text] [PDF]

				S.-G. Wei, Y. Yu, Z.-H. Zhang, and R. B. Felder Angiotensin II upregulates hypothalamic AT1 receptor expression in rats via the mitogen-activated protein kinase pathway Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1425 - H1433. [Abstract] [Full Text] [PDF]

				T. E. Lindley, D. W. Infanger, M. Rishniw, Y. Zhou, M. F. Doobay, R. V. Sharma, and R. L. Davisson Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2009; 296(1): R1 - R8. [Abstract] [Full Text] [PDF]

				S.-G. Wei, Y. Yu, Z.-H. Zhang, R. M. Weiss, and R. B. Felder Mitogen-Activated Protein Kinases Mediate Upregulation of Hypothalamic Angiotensin II Type 1 Receptors in Heart Failure Rats Hypertension, October 1, 2008; 52(4): 679 - 686. [Abstract] [Full Text] [PDF]