Ramiprilat prevents the development of acute coronary endothelial dysfunction in the dog |
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Authors: | PA Martorana H Ruetten B Goebel D Koehl B Roegner BA Schoelkens M Keil |
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Institution: | (1) Hoechst Marion Roussel Deutschland GmbH, Disease Group Cardiovascular Diseases, Building H 821, 65926 Frankfurt/Main, Germany, E-mail: Hartmut.Ruetten@hmrag.com, DE |
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Abstract: | We investigated the effect of an infusion of ramiprilat on the development of coronary endothelial dysfunction. In anesthetized
dogs, the endothelium-dependent vasodilators acetylcholine (ACh, 5 and 10 μg · min−1 for 1 min) and serotonin (5-HT, 50 and 100 μg · min−1 for 1 min) and the endothelium-independent vasodilator nitroglycerin (NTG, 50 and 100 μg · min−1 for 1 min) were given intracoronarily (i.c.) both prior to and after 60 min of ischemia (I) and 180 min of reperfusion R
of a coronary artery. During I/R the dogs received i.c. either saline (N = 22) or ramiprilat (40 ng/kg · min−1, N = 14). At the end of the experiment, a biopsy of the most distal coronary bed was processed for scanning electron microscopy
(SEM). Prior to I/R all vasodilators induced a similar dose-related increase in coronary flow in both groups. Following I/R,
in controls the responses to ACh and 5-HT were significantly blunted (ACh: −39 % and −34 %; 5-HT: −48 % and −49 %); those
to NTG were unchanged. Ramiprilat significantly prevented the blunting of the responses to ACh (−5 %, and −10 %) and 5-HT
(−11 %, and −19 %). SEM of control subepicardial arterioles showed adhesion of leukocytes to the endothelium and crater formation.
No craters were seen in the ramiprilat-treated dogs. Thus, an acute infusion of ramiprilat significantly prevents the development
of coronary endothelial dysfunction. Additionally, the appearance of crater-like changes on the endothelial surface can be
taken as a morphological marker of endothelial dysfunction.
Received: 19 November 1998, Returned for 1. revision: 17 December 1998, 1. Revision received: 18 January 1999, Returned for
2. revision: 10 February 1999, 2. Revision received: 26 February 1999, Accepted: 1 March 1999 |
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Keywords: | Angiotensin converting enzyme inhibition – ischemia and reperfusion – endothelial dysfunction – dog |
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