EFFECT OF 5-HYDROXYTRYPTAMINE ON THE MEMBRANE-POTENTIAL OF ENDOTHELIAL AND SMOOTH-MUSCLE CELLS IN THE PIG CORONARY-ARTERY

1 Many endothelium-dependent vasodilators hyperpolarize the endothelia l cells in blood vessels. It is not known whether these hyperpolarizat ions are linked to nitric oxide synthesis or to an endothelium-derived hyperpolarizing phenomenon, since most of the vasodilators release bo th factors. In this context, we first verified that the endothelium-de pendent relaxations induced by 5-hydroxytryptamine (5-HT) on pig coron ary arteries are due only to the activation of the nitric oxide pathwa y. Then we studied the effects of 5-HT on membrane potential of endoth elial and smooth muscle cells. 2 In the absence of endothelium, 5-HT c aused a concentration-dependent contraction of coronary artery strips. No change of the smooth muscle cell membrane potential was observed d uring contraction to 1 mu M 5-HT. 3 In the presence of 1 mu M ketanser in to suppress the contractile effect of 5-HT, 5-HT induced concentrat ion-dependent relaxation of endothelium-intact strips precontracted by 10 mu M prostaglandin F-2 alpha (PGF(2 alpha)). These relaxations wer e suppressed by 1 mu M N-G-nitro-L-arginine, an inhibitor of nitric ox ide synthesis, showing that they were produced predominantly by nitric oxide. 4 In the presence of 1 mu M ketanserin, 1 mu M 5-HT did not ch ange the smooth muscle cell membrane potential of strips precontracted by either 10 mu M PGF(2 alpha) or by 10 mu M acetylcholine (ACh). In the same conditions, 1 mu M 5-HT caused a weak 2.6 +/- 0.4 mV hyperpol arization, of the endothelial cells. 5 In conclusion, the fact that 5- HT did not change the membrane potential of smooth muscle cells and on ly weakly hyperpolarized the endothelial cells during relaxations, sug gests that in both cell types no electrical events accompany activatio n of the nitric oxide pathway. This is in contrast to the hyperpolariz ations observed in endothelial and smooth muscle cells when the endoth elium-derived hyperpolarization factor (EDHF) pathway is activated.