The third pathway: endothelium-dependent hyperpolarization
Félétou, M.; Vanhoutte, P.M.
Journal of Physiology and Pharmacology An Official Journal of the Polish Physiological Society 50(4): 525-534
1999
ISSN/ISBN: 0867-5910 PMID: 10639003 Document Number: 510138
In response to various neurohumoral substances endothelial cells release nitric oxide (NO), prostacyclin and produce hyperpolarization of the underlying vascular smooth muscle cells, possibly by releasing another factor termed endothelium-derived hyperpolarizing factor (EDHF). EDHF-mediated responses are sensitive to the combination of two toxins, charybdotoxin plus apamin, but do not involve ATP-sensitive or large conductance calcium-activated potassium channels. As hyperpolarization of the endothelial cells is required in order to observe endothelium-dependent hyperpolarization, and electrical coupling through myo-endothelial gap junctions may explain the phenomenon. An alternative explanation is that the hyperpolarization of the endothelial cells causes an efflux of potassium that in turn activates the inwardly rectifying potassium conductance and the Na+/K+ pump of the smooth muscle cells. Endothelial cells produce metabolites of the cytochrome P450-monooxygenase that activate BKCa, and induce hyperpolarization of coronary arterial smooth muscle cells. The elucidation of the mechanism underlying endothelium-dependent hyperpolarization and the discovery of specific inhibitors of the phenomenon are prerequisite for the understanding of the physiological role of this alternative endothelial pathway involved in the control of vascular tone in health and disease.