Jm. Doughty et al., Blockade of chloride channels reveals relaxations of rat small mesenteric arteries to raised potassium, BR J PHARM, 132(1), 2001, pp. 293-301
1 Raised extracellular K+ relaxes some arteries, and has been proposed as E
ndothelium-Derived Hyperpolarizing Factor (EDHF). However, relaxation of ra
t small mesenteric arteries to K+ is highly variable. We have investigated
the mechanism of K+-induced dilatation and relaxation of pressurized arteri
es 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 prese
nce 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 endoth
elium-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 pr
esence of raised [K+](0), 60 mM sucrose and 30 muM Ba2+, 10 muM acetycholin
e still relaxed all arteries.
5 Fifty muM 18 alpha -glycyrrhetinic acid (18 alpha -GA), a gap junction in
hibitor, 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 m
esenteric arteries, using NPPB or hyperosmotic superfusion, reveals a endot
helium-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.