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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/E305    most recent 00512.2007v1 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 Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Chun, T.-Y. Articles by Stier, C. T. Search for Related Content PubMed PubMed Citation Articles by Chun, T.-Y. Articles by Stier, C. T., Jr.

Aldosterone, but not angiotensin II, increases profibrotic factors in kidney of adrenalectomized stroke-prone spontaneously hypertensive rats

¹Department of Medicine, Indiana University School of Medicine, and ²Richard L. Roudebush Department of Veterans Affairs Medical Center, Indianapolis, Indiana; and Departments of ³Pathology and ⁴Pharmacology, New York Medical College, Valhalla, New York

Submitted 7 August 2007 ; accepted in final form 16 May 2008

An increase in angiotensin II (ANG II) under conditions of high salt intake can result in renal damage. The extent to which ANG II does this directly or by way of stimulating aldosterone (Aldo) secretion is a subject of some debate. In the present study, we sought to determine the separate effects of Aldo and ANG II on the expression of plasminogen activator inhibitor-1 (PAI-1) and other factors related to renal fibrosis in the stroke-prone spontaneously hypertensive rat (SHRSP). Saline-drinking male SHRSPs underwent adrenalectomy (ADX) or sham operation (Sham). Treatment groups consisted of ADX + ANG II (25 ng/min sc) and ADX + Aldo (40 µg·kg^–1·day^–1 sc). After 2 wk of treatment, circulating Aldo levels were reduced to the limit of detection, renal PAI-1, transforming growth factor-β1 (TGF-β1), and osteopontin expression, and phospho-Smad2 (p-Smad2) level were decreased severalfold, and Smad7 (an inhibitory regulator of TGF-β1 action) expression was increased in ADX compared with Sham rats. Infusion of Aldo into ADX SHRSPs restored the renal mRNA expression of PAI-1, TGF-β1 (along with restored p-Smad2 level), and osteopontin and reduced that of Smad7, whereas ANG II had no or a lesser effect. The findings were confirmed by histological examination of renal tissue. In summary, in the saline-drinking SHRSP, Aldo increased renal profibrotic factors and produced renal injury whereas ANG II in the absence of the adrenals had no effect.

plasminogen activator inhibitor-1; osteopontin; transforming growth factor-β1