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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.

Coronary endothelial dysfunction is characterized by a lower response to endothelium-dependent vasodilators such as acetylcholine (ACh) and serotonin (5-HT), but by an unaltered response to endothelium-independent vasodilators such as nitroglycerin (NTG). In the present study, we investigated the vasoreactivity of the coronary bed in vivo, in a dog model of ischemia and reperfusion (I/R). We also assessed the morphology of the subepicardial arterioles and capillary bed by means of scanning electron microscopy (SEM). Anesthetized, instrumented dogs were divided in two groups. One group (N=27) was submitted to ischemia (60 min) and reperfusion (180 min) of the left circumflex coronary artery, the second group (N=8) was sham-operated. Prior to and following I/R, ACh, 5-HT, and NTG were given intracoronarily. At the end of the experiment a 1 cm3myocardial biopsy was processed for SEM. The sham-operated dogs showed a reduction of basal coronary flow of 11%, but the vasoreactivity to ACh and 5-HT remained constant. In the I/R group, basal coronary flow was reduced by 35% (p<0.05), and the vasoreactivity to ACh and 5-HT, but not to NTG, was significantly blunted. At SEM the arterioles of the dogs submitted to I/R showed a marked adhesion of leukocytes associated with holes an the endothelial surface, while the capillary bed was free of changes and patent. Thus, following I/R, coronary endothelial dysfunction could be demonstrated in vivo by the blunting of the vasoreactive responses to two different endothelium-dependent vasodilators. The responses to NTG were not affected, probably because the function of the smooth muscle cell was preserved, and the capillary bed was patent.