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Blockade of chloride channels reveals relaxations of rat small mesenteric arteries to raised potassium
Author(s) -
Doughty Joanne M,
Boyle John P,
Langton Philip D
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703769
Subject(s) - mesenteric arteries , chemistry , vasodilation , isometric exercise , anatomy , biophysics , vasoconstriction , acetylcholine , medicine , endocrinology , artery , biology
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 m M 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 (IC 50 : 1.16 μ M ). Relaxations to raised [K + ] o in the presence of NPPB, were abolished by 30 μ M Ba 2+ or endothelial‐denudation. Acetycholine (10 μ M ) relaxed endothelium‐intact arteries in presence of raised [K + ] o NPPB and Ba 2+ . Relaxations to raised [K + ] o were revealed in hyperosmotic superfusate (+60 m M sucrose). These relaxations were abolished by 30 μ M Ba 2+ . In the presence of raised [K + ] o , 60 m M sucrose and 30 μ M Ba 2+ , 10 μ M acetycholine still relaxed all arteries. Fifty μ M 18α‐glycyrrhetinic acid (18α‐GA), a gap junction inhibitor, depressed relaxations to both 10 μ M acetylcholine and raised [K + ] o , in the presence of 10 μ M NPPB. In summary, blockade of a volume‐sensitive Cl − conductance in small rat mesenteric arteries, using NPPB or hyperosmotic superfusion, reveals a endothelium‐dependent, Ba 2+ 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