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Essential Role of EDHF in the Initiation and Maintenance of Adrenergic Vasomotion in Rat Mesenteric Arteries

Essential Role of EDHF in the Initiation and Maintenance of Adrenergic Vasomotion in Rat Mesenteric Arteries

Joseph R H Mauban, W Gil Wier

Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H608-16.

PMID: 15059779

Abstract:

The possible roles of endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)), nitric oxide (NO), arachidonic acid (AA) metabolites, and Ca(2+)-activated K(+) (K(Ca)) channels in adrenergically induced vasomotion were examined in pressurized rat mesenteric arteries. Removal of the endothelium or buffering [Ca(2+)](i) selectively in endothelial cells with BAPTA eliminated vasomotion in response to phenylephrine (PE; 10.0 microM). In arteries with intact endothelium, inhibition of NO synthase with N(omega)-nitro-l-arginine methyl ester (l-NAME; 300.0 microM) or N(omega)-nitro-l-arginine (l-NNA; 300.0 microM) did not eliminate vasomotion. Neither inhibition of cGMP formation with 10.0 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) nor inhibition of prostanoid formation (10.0 microM indomethacin) eliminated vasomotion. Similarly, inhibition of AA cytochrome P-450 metabolism with an intraluminal application of 17-octadecynoic acid (17-ODYA) or 6-(2-propargyloxyphenyl)hexanoic acid (PPOH) failed to eliminate vasomotion. In contrast, intraluminal application of the K(Ca) channel blockers apamin (250.0 nM) and charybdotoxin (100.0 nM), together, abolished vasomotion and changed synchronous Ca(2+) oscillations in smooth muscle cells to asynchronous propagating Ca(2+) waves. Apamin, charybdotoxin, or iberiotoxin (100.0 nM) alone did not eliminate vasomotion, nor did the combination of apamin and iberiotoxin. The results show that adrenergic vasomotion in rat mesenteric arteries is critically dependent on Ca(2+)-activated K(+) channels in endothelial cells. Because these channels (small- and intermediate-conductance K(Ca) channels) are a recognized component of EDHF, we conclude therefore that EDHF is essential for the development of adrenergically induced vasomotion.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP206052019	6-(2-Propargyloxyphenyl)hexanoic acid		206052-01-9	Price

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