Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries

Abstract

We studied quantitative aspects of coronary artery contraction in isolated epicardial coronary ring segments from 49 human hearts. The order of maximal tension developed by drugs in normal calcium (ionized calcium, 1.26 mM) solution was U-44069 (a prostaglandin endoperoxide analog) greater than histamine greater than carbachol greater than serotonin greater than phenylephrine greater than ergonovine. In Ca2+-free solution these same drugs mediated a lesser degree of contraction, which demonstrates that the human coronary artery uses both "intracellular" and "extracellular" calcium in hormone receptor-activated contraction. U-44069, histamine, carbachol, and phenylephrine produced calcium-free/normal calcium maximal responses of 62.9% 48.7%, 39.8%, and 37.2%, respectively. Morphologic characteristics of the atherosclerotic plaques within the vessel lumen and the degree of myocardial dysfunction did not qualitatively alter these contractile responses. However, severely atherosclerotic coronary segments were supersensitive to histamine, but not to carbachol or calcium. In conclusion, the human epicardial coronary artery is a highly reactive vessel that uses at least two calcium pools to couple contraction. Receptor-coupled agonists differ in their abilities to mediate contraction and in the degree to which each calcium pool is used, and the presence of atherosclerosis potentiates the contractile response to histamine.