Abstract
1. Many endothelium-dependent vasodilators hyperpolarize the endothelial cells in blood vessels. It is not known whether these hyperpolarizations are linked to nitric oxide synthesis or to an endothelium-derived hyperpolarizing phenomenon, since most of the vasodilators release both factors. In this context, we first verified that the endothelium-dependent relaxations induced by 5-hydroxytryptamine (5-HT) on pig coronary arteries are due only to the activation of the nitric oxide pathway. Then we studied the effects of 5-HT on membrane potential of endothelial and smooth muscle cells. 2. In the absence of endothelium, 5-HT caused a concentration-dependent contraction of coronary artery strips. No change of the smooth muscle cell membrane potential was observed during contraction to 1 microM 5-HT. 3. In the presence of 1 microM ketanserin to suppress the contractile effect of 5-HT, 5-HT induced concentration-dependent relaxation of endothelium-intact strips precontracted by 10 microM prostaglandin F2 alpha (PGF2 alpha). These relaxations were suppressed by 1 microM NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, showing that they were produced predominantly by nitric oxide. 4. In the presence of 1 microM ketanserin, 1 microM 5-HT did not change the smooth muscle cell membrane potential of strips precontracted by either 10 microM PGF2 alpha or by 10 microM acetylcholine (ACh). In the same conditions, 1 microM 5-HT caused a weak 2.6 +/- 0.4 mV hyperpolarization, of the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Angus J. A. 5-HT receptors in the coronary circulation. Trends Pharmacol Sci. 1989 Mar;10(3):89–90. doi: 10.1016/0165-6147(89)90197-1. [DOI] [PubMed] [Google Scholar]
- Bax W. A., Renzenbrink G. J., Van Heuven-Nolsen D., Thijssen E. J., Bos E., Saxena P. R. 5-HT receptors mediating contractions of the isolated human coronary artery. Eur J Pharmacol. 1993 Aug 3;239(1-3):203–210. doi: 10.1016/0014-2999(93)90995-t. [DOI] [PubMed] [Google Scholar]
- Beny J. L., Brunet P. C., Huggel H. Effect of mechanical stimulation, substance P and vasoactive intestinal polypeptide on the electrical and mechanical activities of circular smooth muscles from pig coronary arteries contracted with acetylcholine: role of endothelium. Pharmacology. 1986;33(2):61–68. doi: 10.1159/000138202. [DOI] [PubMed] [Google Scholar]
- Beny J. L., Brunet P., Huggel H. Interaction of bradykinin and des-Arg9-bradykinin with isolated pig coronary arteries: mechanical and electrophysiological events. Regul Pept. 1987 Apr;17(4):181–190. doi: 10.1016/0167-0115(87)90061-9. [DOI] [PubMed] [Google Scholar]
- Brunet P. C., Bény J. L. Substance P and bradykinin hyperpolarize pig coronary artery endothelial cells in primary culture. Blood Vessels. 1989;26(4):228–234. doi: 10.1159/000158770. [DOI] [PubMed] [Google Scholar]
- Bruning T. A., Chang P. C., Blauw G. J., Vermeij P., van Zwieten P. A. Serotonin-induced vasodilatation in the human forearm is mediated by the "nitric oxide-pathway": no evidence for involvement of the 5-HT3-receptor. J Cardiovasc Pharmacol. 1993 Jul;22(1):44–51. doi: 10.1097/00005344-199307000-00008. [DOI] [PubMed] [Google Scholar]
- Bény J. L., Brunet P. C. Neither nitric oxide nor nitroglycerin accounts for all the characteristics of endothelially mediated vasodilatation of pig coronary arteries. Blood Vessels. 1988;25(6):308–311. [PubMed] [Google Scholar]
- Bény J. L., Connat J. L. An electron-microscopic study of smooth muscle cell dye coupling in the pig coronary arteries. Role of gap junctions. Circ Res. 1992 Jan;70(1):49–55. doi: 10.1161/01.res.70.1.49. [DOI] [PubMed] [Google Scholar]
- Bény J. L. Effect of substance P on the membrane potential of coronary arterial endothelial cells in situ. Agents Actions. 1990 Nov;31(3-4):317–320. doi: 10.1007/BF01997626. [DOI] [PubMed] [Google Scholar]
- Bény J. L. Endothelial and smooth muscle cells hyperpolarized by bradykinin are not dye coupled. Am J Physiol. 1990 Mar;258(3 Pt 2):H836–H841. doi: 10.1152/ajpheart.1990.258.3.H836. [DOI] [PubMed] [Google Scholar]
- Bény J. L., Gribi F. Dye and electrical coupling of endothelial cells in situ. Tissue Cell. 1989;21(6):797–802. doi: 10.1016/0040-8166(89)90030-x. [DOI] [PubMed] [Google Scholar]
- Bény J. L., Pacicca C. Bidirectional electrical communication between smooth muscle and endothelial cells in the pig coronary artery. Am J Physiol. 1994 Apr;266(4 Pt 2):H1465–H1472. doi: 10.1152/ajpheart.1994.266.4.H1465. [DOI] [PubMed] [Google Scholar]
- Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
- Cohen R. A., Shepherd J. T., Vanhoutte P. M. 5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries. Am J Physiol. 1983 Dec;245(6):H1077–H1080. doi: 10.1152/ajpheart.1983.245.6.H1077. [DOI] [PubMed] [Google Scholar]
- Garland C. J. The role of membrane depolarization in the contractile response of the rabbit basilar artery to 5-hydroxytryptamine. J Physiol. 1987 Nov;392:333–348. doi: 10.1113/jphysiol.1987.sp016783. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houston D. S., Vanhoutte P. M. Serotonin and the vascular system. Role in health and disease, and implications for therapy. Drugs. 1986 Feb;31(2):149–163. doi: 10.2165/00003495-198631020-00004. [DOI] [PubMed] [Google Scholar]
- Ito Y., Kitamura K., Kuriyama H. Effects of acetylcholine and catecholamines on the smooth muscle cell of the porcine coronary artery. J Physiol. 1979 Sep;294:595–611. doi: 10.1113/jphysiol.1979.sp012948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itoh T. Pharmacomechanical coupling in vascular smooth muscle cells--an overview. Jpn J Pharmacol. 1991 Jan;55(1):1–9. doi: 10.1254/jjp.55.1. [DOI] [PubMed] [Google Scholar]
- Kilpatrick E. V., Cocks T. M. Evidence for differential roles of nitric oxide (NO) and hyperpolarization in endothelium-dependent relaxation of pig isolated coronary artery. Br J Pharmacol. 1994 Jun;112(2):557–565. doi: 10.1111/j.1476-5381.1994.tb13110.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Komori K., Lorenz R. R., Vanhoutte P. M. Nitric oxide, ACh, and electrical and mechanical properties of canine arterial smooth muscle. Am J Physiol. 1988 Jul;255(1 Pt 2):H207–H212. doi: 10.1152/ajpheart.1988.255.1.H207. [DOI] [PubMed] [Google Scholar]
- Leysen J. E., Awouters F., Kennis L., Laduron P. M., Vandenberk J., Janssen P. A. Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981 Mar 2;28(9):1015–1022. doi: 10.1016/0024-3205(81)90747-5. [DOI] [PubMed] [Google Scholar]
- Lückhoff A., Busse R. Calcium influx into endothelial cells and formation of endothelium-derived relaxing factor is controlled by the membrane potential. Pflugers Arch. 1990 May;416(3):305–311. doi: 10.1007/BF00392067. [DOI] [PubMed] [Google Scholar]
- Molderings G. J., Engel G., Roth E., Göthert M. Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery. Naunyn Schmiedebergs Arch Pharmacol. 1989 Sep;340(3):300–308. doi: 10.1007/BF00168514. [DOI] [PubMed] [Google Scholar]
- Pacicca C., von der Weid P. Y., Beny J. L. Effect of nitro-L-arginine on endothelium-dependent hyperpolarizations and relaxations of pig coronary arteries. J Physiol. 1992 Nov;457:247–256. doi: 10.1113/jphysiol.1992.sp019376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ratz P. H., Flaim S. F. Acetylcholine- and 5-hydroxytryptamine-stimulated contraction and calcium uptake in bovine coronary arteries: evidence for two populations of receptor-operated calcium channels. J Pharmacol Exp Ther. 1985 Sep;234(3):641–647. [PubMed] [Google Scholar]
- Richard V., Tanner F. C., Tschudi M., Lüscher T. F. Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. Am J Physiol. 1990 Nov;259(5 Pt 2):H1433–H1439. doi: 10.1152/ajpheart.1990.259.5.H1433. [DOI] [PubMed] [Google Scholar]
- Schilling W. P. Effect of membrane potential on cytosolic calcium of bovine aortic endothelial cells. Am J Physiol. 1989 Sep;257(3 Pt 2):H778–H784. doi: 10.1152/ajpheart.1989.257.3.H778. [DOI] [PubMed] [Google Scholar]
- Schoeffter P., Hoyer D. 5-Hydroxytryptamine (5-HT)-induced endothelium-dependent relaxation of pig coronary arteries is mediated by 5-HT receptors similar to the 5-HT1D receptor subtype. J Pharmacol Exp Ther. 1990 Jan;252(1):387–395. [PubMed] [Google Scholar]
- Van Nueten J. M., Janssen P. A., Van Beek J., Xhonneux R., Verbeuren T. J., Vanhoutte P. M. Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther. 1981 Jul;218(1):217–230. [PubMed] [Google Scholar]
- Vanhoutte P. M. Cardiovascular effects of serotonin. J Cardiovasc Pharmacol. 1987;10 (Suppl 3):S8–11. [PubMed] [Google Scholar]
- Vanhoutte P. M., Cohen R. A., Van Nueten J. M. Serotonin and arterial vessels. J Cardiovasc Pharmacol. 1984;6 (Suppl 2):S421–S428. doi: 10.1097/00005344-198406002-00017. [DOI] [PubMed] [Google Scholar]
- von der Weid P. Y., Bény J. L. Simultaneous oscillations in the membrane potential of pig coronary artery endothelial and smooth muscle cells. J Physiol. 1993 Nov;471:13–24. doi: 10.1113/jphysiol.1993.sp019888. [DOI] [PMC free article] [PubMed] [Google Scholar]