Endothelial cells and the electrical and mechanical responses of the rabbit coronary artery to 5-hydroxytryptamine

CJ Garland

The influence of endothelial cells on the response of smooth muscle in the rabbit coronary artery to 5-hydroxytryptamine (5-HT) was investigated with intracellular microelectrode and mechanical methods. Recent work has suggested that 5-HT stimulates the release of a smooth muscle relaxing factor from endothelial cells, which will reduce the direct constrictor action of 5-HT on the artery wall. In arteries with intact endothelial cells, 5-HT (10(-8) to 10(-4) M) produced dose- dependent depolarization of muscle cells in the inner part of the media. Hyperpolarization to 5-HT was not observed, even with 1 microM ketanserin (a 5-HT2 receptor antagonist) present to reduce its direct action on the smooth muscle. After removal of the endothelium 5-HT produced similar sized depolarization, but the graded depolarization was now often accompanied by rhythmical oscillations in membrane potential. Isolated, perfused arteries with an intact endothelium were insensitive to the constrictor action of 5-HT and at wall tensions similar to that in vivo did not show dilatation, even with ketanserin present. Small dilator responses to 5-HT could be recorded in the presence of increased tone to K-rich saline (30 mM). After removal of the endothelium, the mechanical responsiveness greatly increased and 5- HT produced large constrictor responses. The findings suggest that an endothelial-released factor protects the coronary artery from 5-HT which reaches it from the intimal surface and that this protective role could in part be due to inhibition of rhythmical electrical activity in the smooth muscle.

Volume 233, Issue 1, pp. 158-162, 04/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics