Effect of k+ channel blockers on ach-induced hyperpolarization and
relaxation in rat mesenteric arteries.
Chen, Guifa, and Donald W. Cheung.
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa K1Y
4E9, CANADA
APStracts 3:0539H, 1996.
Acetylcholine (ACh) induced endothelium-dependent hyperpolarization in
the rat mesenteric artery in the presence of the nitric oxide
synthase inhibitor N-nitro-L-arginine. We have now studied the
effects of K+ channel blockers on the hyperpolarization responses to
ACh in resting and noradrenaline-contracted rat mesenteric arteries.
We also measured tension simultaneously to determine if the
inhibitory effects of these agents on relaxation could be correlated
to their effects on hyperpolarization. Glibenclamide had no
significant effect on the hyperpolarization or relaxation. TEA (5 mM)
inhibited the hyperpolarization to ACh significantly to a similar
extent in both the resting and noradrenaline-stimulated arteries.
Charybdotoxin (100-150 nM) caused only a small but significant
inhibition. Apamin (0.3 [mu]M) was the most effective in inhibiting
the hyperpolarization in resting arteries. It was less effective in
the noradrenaline-contracted arteries. A combination of apamin and
charybdotoxin completely abolished the hyperpolarization responses in
both conditions. The relaxation to ACh was correlated to
hyperpolarization. In all cases, the inhibition of the relaxation by
the K+ channel blockers could be accounted for by their effects on
the hyperpolarization. These results indicate that calcium-activated
K+ channels, especially those sensitive to apamin, may be the major
ion channels mediating endothelium-dependent hyperpolarization to
ACh.
Received 8 July 1996; accepted in final form 3 December 1996.
APS Manuscript Number H597-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996