Effect of nisoldipine on contractions evoked by endothelin-1 in human isolated distal and proximal coronary arteries and veins.

Abstract

We investigated the differences in the vasoconstrictor effect of endothelin-1 (ET-1) on small and large human coronary arteries and veins and blockade of ET's action with calcium antagonists. Rings from distal and proximal human coronary arteries and veins were suspended in organ baths and exposed to graded concentrations of ET-1 (0.1-30 nM). Coronary veins were the most sensitive to the constrictor action of ET-1. In addition, distal coronary arteries were more sensitive than proximal arteries (EC50 value-log M: 8.92 +/- 0.05 and 8.34 +/- 0.1, respectively). In proximal arteries, incubation with subthreshold concentrations of ET (300 pM) potentiated the vasoconstrictor effect of serotonin 1 microM (115 +/- 2.6% over contractile level before incubation). This potentiated contraction was fully blocked by nisoldipine, a calcium antagonist. In contrast, this potentiation was not observed in human coronary veins. Nisoldipine partly antagonized the contraction evoked by ET-1 in human coronary arteries, but ET-contracted coronary veins were completely resistant to calcium channel blockade. Low concentrations of ET-1 approximating reported circulating levels result in significant contraction of human coronary veins and potentiate the constrictor effect of serotonin in coronary arteries. The blocking effect of the calcium antagonist nisoldipine varies among distal and proximal coronary arteries and veins, suggesting a different mechanism of contraction for ET-1 among these vessels. Because of the suspected role of ET-1 in coronary ischemic syndromes, this differential sensitivity may have important therapeutic implications.