title: Ramiprilat prevents the development of acute coronary endothelial dysfunction in the dog.
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 microg x min(-1) for 1 min) and serotonin (5-HT, 50 and 100 microg x min(-1) for 1 min) and the endothelium-independent vasodilator nitroglycerin (NTG, 50 and 100 microg x 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 x 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.
authors.affiliation: Hoechst Marion Roussel Deutschland GmbH, Disease Group Cardiovascular Diseases, Frankfurt/Main, Germany.
authors.forename: P A
authors.initials: PA
authors.lastname: Martorana
authors.forename: H
authors.initials: H
authors.lastname: Ruetten
authors.forename: B
authors.initials: B
authors.lastname: Goebel
authors.forename: D
authors.initials: D
authors.lastname: Koehl
authors.forename: B
authors.initials: B
authors.lastname: Roegner
authors.forename: B A
authors.initials: BA
authors.lastname: Schoelkens
authors.forename: M
authors.initials: M
authors.lastname: Keil
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D008855:Microscopy, Electron, Scanning; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; D017257:Ramipril