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

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Abstract
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. 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). Relaxations to raised [K+]o in the presence of NPPB, were abolished by 30 μM Ba2+ or endothelial‐denudation. Acetycholine (10 μM) relaxed endothelium‐intact arteries in presence of raised [K+]o NPPB and Ba2+. 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. 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. 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+]o. We conclude that inwardly rectifying potassium channels on the endothelium underlie relaxations to raised [K+]o in rat small mesenteric arteries. British Journal of Pharmacology (2001) 132, 293–301; doi:10.1038/sj.bjp.0703769