Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability.

Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Research Abstract Details 

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Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Abstract Text:

Toshio Imanishi,Hideyuki Ikejima,Hiroto Tsujioka,Akio Kuroi,Katsunobu Kobayashi,Yasuteru Muragaki,Seiichi Mochizuki,Masami Goto,Kiyoshi Yoshida,Takashi Akasaka,

Angiotensin II and aldosterone both promote endothelial dysfunction and atherosclerosis. We investigated the effect of a combination of eplerenone, a selective aldosterone antagonist, and enalapril, an angiotensin-converting enzyme inhibitor, on NO bioavailability and spontaneous atherosclerotic changes. Twenty-four myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), eplerenone (50 mg/kg per day), enalapril (3 mg/kg per day), or eplerenone plus enalapril for 8 weeks (n=6 in each group). After treatment, acetylcholine-induced NO production was measured as a surrogate for endothelium-protective function, and vascular peroxynitrite (a product of superoxide and NO) was measured to assess dysfunctional endothelial NO synthase activity. Plaque area was quantified by histology. Intra-aortic infusion of acetylcholine produced an increase in plasma NO concentration that was significantly higher with all of the drug treatments compared with the control. Eplerenone and enalapril, in combination, increased acetylcholine-induced NO by 7.9 nM, which was significantly higher than with either eplerenone or enalapril alone. Vascular peroxynitrite was significantly higher in the control group (1.3 pmol/mg of protein) and significantly lower with combination treatment (0.4 pmol/mg of protein) compared with the enalapril or eplerenone group. The highest tetrahydrobiopterin levels were observed after cotreatment with eplerenone and enalapril. Histology of the thoracic aorta showed a significantly decreased plaque area with combination therapy compared with monotherapy. Combined treatment with a selective aldosterone antagonist and an angiotensin-converting enzyme inhibitor has additive protective effects on endothelial function and on atherosclerotic changes via decreased nitrosative stress.

Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Publishing Authors By Initials

T Imanishi,H Ikejima,H Tsujioka,A Kuroi,K Kobayashi,Y Muragaki,S Mochizuki,M Goto,K Yoshida,T Akasaka,

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Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hypertension

VOLUME: 51

Page Numbers: 734-41

Journal Abbreviation: Hypertension

ISSN: 1524-4563

DAY: 28

MONTH: 01

YEAR: 2008

Addition of eplerenone to an Angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Information

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LANGUAGE: eng

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AFFILIATION: Correspondence Toshio Imanishi, Department of Cardiovascular Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, Wakayama 641-8510, Japan. t-imani@wakayama-med.ac.jp.

Country: United States

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MEDLINETA: Hypertension

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