In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 77, No. 7 ( 1999-08-01), p. 481-489
Abstract:
The hyperpolarizing factor that is liberated by vascular endothelial cells in response to various agonists, and known to induce relaxation by opening of smooth muscle K + channels, has been suggested to be a product of cytochrome P450 dependent arachidonic acid metabolism. In this study, the direct influence of two phospholipase A 2 inhibitors and of five structurally and mechanistically different cytochrome P450 inhibitors on K + currents in freshly isolated vascular smooth muscle cells from the rat aorta was investigated. On stepping the cell membrane potential from -70 mV to a series of depolarized test potentials, a noisy outward current developed at test potentials 〉 +10 mV, which showed no appreciable inactivation during the voltage pulse. It was largely abolished by 3 mM external tetraethylammonium chloride (TEA), suggesting that it predominantly consisted of current through large-conductance Ca 2+ -activated K + channels. The phospholipase A 2 inhibitor quinacrine considerably inhibited this TEA-sensitive current, while 4-bromophenacylbromide exerted no effect. The cytochrome P450 inhibitors proadifen and miconazole reversibly decreased the amplitude of I K , while clotrimazole and 1-aminobenzotriazole had no effect. Conversely, 17-octadecynoic acid increased whole-cell I K . These results show that some phospholipase A 2 and cytochrome P450 inhibitors may interfere with K + channel activation in the rat arterial smooth muscle cell. The relevance of these findings to studies on the involvement of cytochrome P450 dependent metabolism in the generation of the endothelium-derived hyperpolarizing factor in intact arteries is discussed.Key words: endothelial factors, smooth muscle, membrane currents, vasodilation, endothelium-derived hyperpolarizing factor (EDHF), arachidonic acid.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
1999
detail.hit.zdb_id:
2004356-9
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