Ramiprilat prevents the development of acute coronary endothelial dysfunction in the dog

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 mu g . min(-1) for 1 mi n) and serotonin (5-HT, 50 and 100 mu g . - min(-1) for 1 min) and the endo thelium-independent vasodilator nitroglycerin (NTG, 50 and 100 mu g . 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. Du ring 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). P rior to I/R all vasodilators induced a similar dose-related increase in cor onary 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 -4 9%); those to NTG were unchanged. Ramiprilat significantly prevented the bl unting of the responses to ACh (-5%, and -10%) and 5-HT (-11%, and -19%). S EM of control subepicardial arterioles showed adhesion of leukocytes to the endothelium and crater formation. No craters were seen in the ramiprilat-t reated dogs. Thus, an acute infusion of ramiprilat significantly prevents t he development of coronary endothelial dysfunction. Additionally the appear ance of crater-like changes on the endothelial surface can be taken as a mo rphological marker of endothelial dysfunction.