Selective hypercontraction caused by ergonovine in the canine coronary artery under conditions of induced atherosclerosis

Abstract

The relationship between the hypercontractile response of the regional coronary artery to ergonovine and induced vascular change after endothelial denudation and a high-cholesterol diet was examined in dogs by arteriographic (in situ) and mechanographic (in vitro) methods. In 15 mongrel dogs, selective endothelial denudation of either the left circumflex coronary artery (LCX) or left anterior descending coronary artery (LAD) was repeated twice 1 month apart by means of coronary arterial catheterization. A high-cholesterol diet (20 g/day) was given thereafter for 3 (n = 15) and 6 (n = 8) months. Although there was no difference in the extent of coronary vasoconstriction between the LAD and LCX before or immediately after endothelial denudation, after intravenous administration of ergonovine a significant augmentation of coronary constriction along the denuded portion was noted arteriographically in the long-term phase (1 to 6 months). At the end of the study in vivo, isometric tension of the strips of the denuded and contralateral intact coronary arteries was measured during the cumulative addition of ergonovine, serotonin, or phenylephrine to the organ bath; agonist responses were standardized by the response to 35 mM KCl. Although the concentration-response relations for phenylephrine (10(-9) M to 10(-5) M) were not significantly different between intact and denuded arteries, responses of the denuded portion to cumulative addition of ergonovine (10(-10) M) or serotonin 10(-9) M to 10(-5) M) exhibited markedly depressed threshold concentrations along with a significantly lowered negative logarithm (pD2) of the dose producing 50% of the maximum effect. The tension developed in the denuded portion was also enhanced over that noted in the contralateral coronary artery during the cumulative addition of ergonovine but not during application of phenylephrine. Thus enhanced constriction documented arteriographically may be derived from the localized hypersensitivity to ergonovine. Microscopically, the endothelial denudation and a long-term high-cholesterol diet resulted in a regional intimal thickening with fibrous proliferation but little lipid deposition. Therefore smooth muscle in atherosclerotic arteries may be hypersensitive to specific agonists such as ergonovine and serotonin in a canine preparation. These results suggest that coronary spasm induced by ergonovine in humans is relevant to the presence of atherosclerotic changes in the vascular wall.