Blockade of chloride channels reveals relaxations of rat small mesenteric arteries to raised potassium

Abstract

1. Raised extracellular K+ relaxes some arteries, and has been proposed as Endothelium-Derived Hyperpolarizing Factor (EDHF). However, relaxation of rat small mesenteric arteries to K+ is highly variable. We have investigated the mechanism of K+-induced dilatation and relaxation of pressurized arteries and arteries mounted for measurement of isometric force. 2. Raising [K+]o from 5.88-10.58 mM did not dilate or relax pressurized or isometric arteries. Relaxation to raised [K+]o was revealed in the presence of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB); this effect of NPPB was concentration-dependent (IC50:1.16 μM). 3. Relaxations to raised [K+]o in the presence of NPPB, were abolished by 30 μM Ba2+ or endothelial-denudation. Acetycholine (10μM) relaxed endothelium-intact arteries in presence of raised [K+]o NPPB and Ba2+. 4. Relaxations to raised [K+]o were revealed in hyperosmotic superfusate (+ 60 mM sucrose). These relaxations were abolished by 30 μM Ba2+. In the presence of raised [K+]o, 60 mM sucrose and 30 μM Ba2+, 10 μM acetycholine still relaxed all arteries. 5. Fifty μM 18α-glycyrrhetinic acid (18α-GA), a gap junction inhibitor, depressed relaxations to both 10 μM acetylcholine and raised [K+]o, in the presence of 10 μM NPPB. 6. In summary, blockade of a volume-sensitive C1- conductance in small rat mesenteric arteries, using NPPB or hyperosmotic superfusion, reveals a endothelium-dependent, Ba2+ sensitive dilatation or relaxation of rat mesenteric arteries to raised [K+]o. We conclude that inwardly rectifying potassium channels on the endothelium underlie relaxations to raised [K+]o in rat small mesenteric arteries.