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: 293/5/F1584    most recent 00124.2007v1 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Ortiz, R. M. Articles by Mitchell, K. D. Search for Related Content PubMed PubMed Citation Articles by Ortiz, R. M. Articles by Mitchell, K. D.

Aldosterone receptor antagonism alleviates proteinuria, but not malignant hypertension, in Cyp1a1-Ren2 transgenic rats

¹Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana; and ²Centre for Cardiovascular Science, The University of Edinburgh Medical School, Edinburgh, United Kingdom

Submitted 15 March 2007 ; accepted in final form 13 August 2007

The contribution of elevated aldosterone to the pathogenesis of malignant, ANG II-dependent hypertension remains uncertain. Therefore, we examined whether chronic mineralocorticoid receptor blockade attenuates the development of malignant hypertension in transgenic rats (TGRs) with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Systolic blood pressure (SBP) was measured by radiotelemetry in male TGRs in three groups: 1) control (n = 9), 2) hypertensives (HT; n = 8), and 3) hypertensives + spironolactone (11 mg·kg^–1·day^–1 sc; HTS; n = 8). Malignant hypertension was induced with dietary indole-3-carbinol (0.3%) for 10 days. Metabolic measurements were taken at the beginning of the study and at days 2 and 9. HT exhibited elevated SBP (125 ± 3 vs. 187 ± 5 mmHg), plasma renin activity (5 ± 1 vs. 29 ± 10 ng ANG I·ml^–1·h^–1), plasma ANG II (175 ± 39 vs. 611 ± 74 fmol/ml), and plasma aldosterone (0.31 ± 0.04 vs. 5.42 ± 1.02 nmol/l). Urinary aldosterone excretion increased 5.5-fold by day 2 and an additional 90% by day 9. HT was associated with a 1.8-fold increase in proteinuria by day 9 that was alleviated by treatment with spironolactone (25 ± 5 vs. 13 ± 3 mg/day), suggesting that aldosterone contributes to the renal damage observed in malignant hypertension. Urinary Na⁺ excretion was decreased 76% on day 2, despite a sixfold increase in urinary aldosterone excretion. Decrease in urinary Na⁺ excretion on day 2 in HT suggests that Na⁺ reabsorption was increased in response to the increase in aldosterone; however, the lack of a change in SBP between HT and HTS suggests that mechanisms independent of aldosterone stimulation make a greater contribution to the maintenance of elevated arterial pressure in malignant hypertension in Cyp1a1-Ren2 transgenic rats.

angiotensin II; eplerenone; pressure natriuresis; spironolactone

This article has been cited by other articles:

				X. Liu, C. O. C. Bellamy, M. A. Bailey, L. J. Mullins, D. R. Dunbar, C. J. Kenyon, G. Brooker, S. Kantachuvesiri, K. Maratou, A. Ashek, et al. Angiotensin-converting Enzyme Is a Modifier of Hypertensive End Organ Damage J. Biol. Chem., June 5, 2009; 284(23): 15564 - 15572. [Abstract] [Full Text] [PDF]

				R. M. Ortiz Delineating the contributions of AT1a and AT1b receptor-mediated uptake of ANG II in kidneys and adrenals Am J Physiol Renal Physiol, February 1, 2008; 294(2): F291 - F292. [Full Text] [PDF]