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Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

Department of Cardiology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands, l.j.wagenaar{at}thorax.azg.nl, Department of Clinical Pharmacology, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands

Hendrik Buikema

Department of Clinical Pharmacology, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands

Yigal M Pinto

Department of Cardiology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

Wiek H van Gilst

Department of Cardiology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands, Department of Clinical Pharmacology, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT₁-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF.

CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor N_G-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO).

ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO.

Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.

Key Words: rats • myocardial infarction • heart failure • endothelial function • ACE-inhibition • AT1-receptor blockade • oxidative stress

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S64-S69 (2001)
DOI: 10.1177/14703203010020011101


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This Article Abstract Free Full Text (Free PDF) Free 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 Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Wagenaar, L. J Articles by van Gilst, W. H Search for Related Content PubMed Articles by Wagenaar, L. J Articles by van Gilst, W. H Social Bookmarking                         What's this?