Eplerenone decreases inflammatory foci in spontaneously hypertensive rat hearts with minimal effects on blood pressure

Journal of Cardiovascular Pharmacology
Philip E BrandishJames C Hershey

Abstract

The blood pressure (BP)-lowering effects of mineralocorticoid receptor (MR) antagonists in salt-sensitive rat models of hypertension are well understood. However, studies in salt-independent models have yielded mixed results, and therefore, we measured the hemodynamic effects of MR blockade in spontaneously hypertensive rats. We treated spontaneously hypertensive rats for 8 weeks with 30-300 mg.kg.d eplerenone or 20 mg.kg.d losartan and monitored BP using radiotelemetry and performed histopathological analyses of the hearts. Eplerenone, in contrast to losartan, caused only a small reduction in systolic BP at the highest dose tested. Both reduced left ventricular wall thickness, although eplerenone was less effective than losartan. Only losartan decreased heart weight. We observed foci of cardiomyopathy characterized by combinations of infiltrating monocytes, necrotic myocytes, and interstitial fibrosis in hearts of control animals. The number of foci seemed to be decreased in hearts of losartan- and eplerenone-treated animals. In a second study, using quantitative histomorphometry, the number of foci was significantly reduced by 20 mg.kg.d losartan (by 68%) or by 300 mg.kg.d eplerenone (by 50%). Our data support the hypothesis ...Continue Reading

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Citations

Jan 18, 2013·Expert Opinion on Therapeutic Targets·Morag J Young
Jul 21, 2011·Molecular and Cellular Endocrinology·Peter Kolkhof, Steffen A Borden
Mar 14, 2014·Journal of Cardiovascular Pharmacology·Peter KolkhofStefan Schäfer

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