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

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+](0) from 5.88-10.58 mM did not dilate or relax pressurized or isometric arteries. Relaxation to raised [K+](0) was revealed in the presence of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB); this effect of NPPB was concentration-dependent (IC50: 1.16 muM). 3 Relaxations to raised [K+](0) in the presence of NPPB, were abolished by 30 muM Ba2+ or endothelial-denudation. Acetycholine (10 muM) relaxed endothelium-intact arteries in presence of raised [K+](0) NPPB and Ba2+. 4 Relaxations to raised [K+](0) were revealed in hyperosmotic superfusate (+60 mM sucrose). These relaxations were abolished by 30 muM Ba2+. In the presence of raised [K+](0), 60 mM sucrose and 30 muM Ba2+, 10 muM acetycholine still relaxed all arteries. 5 Fifty muM 18 alpha -glycyrrhetinic acid (18 alpha -GA), a gap junction inhibitor, depressed relaxations to both 10 muM acetylcholine and raised [K+](0), in the presence of 10 muM NPPB. 6 In summary, blockade of a volume-sensitive Cl- 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+](0). We conclude that inwardly rectifying potassium channels on the endothelium underlie relaxations to raised [K+](0) in rat small mesenteric arteries.