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Vol. 285, Issue 2, 659-664, May 1998
Department of Pharmacology (P.M., D.F., J.C.Mc.), New York Medical
College, Valhalla, New York, and
Department of Cell Biology (J.Q.),
University of Medicine and Dentistry of New Jersey, School of
Osteopathic Medicine, Stratford, New Jersey
The role of K+ channels in the nitric oxide-independent
renal vasodilator effect of acetylcholine (Ach) was examined to address the hypothesis that the mechanism underlying this response was different from that of bradykinin, because an earlier study indicated the possibility of different mediators. We used the rat isolated, perfused kidney that was constricted with phenylephrine and treated with nitroarginine and indomethacin to inhibit nitric oxide synthase and cyclooxygenase, respectively. The nonspecific K+
channel inhibitors, procaine and tetraethylammonium (TEA), reduced vasodilator responses to Ach and cromakalim, but not those to nitroprusside. Glibenclamide, an inhibitor of ATP-sensitive
K+ channels, reduced vasodilator responses to cromakalim
but did not affect those to Ach or nitroprusside. Charybdotoxin, an
inhibitor of Ca++-activated K+ channels,
reduced vasodilator responses to Ach without affecting those to
cromakalim or nitroprusside. Iberiotoxin and apamin, inhibitors of
large- and small-conductance Ca++-activated K+
channels, respectively, did not reduce vasodilation induced by Ach,
cromakalim or nitroprusside. The inhibitor of cytochrome P450,
clotrimazole, reduced the renal vasodilator effects of Ach and
bradykinin but not those of nitroprusside or SCA 40, an agonist for
Ca++-activated K+ channels. These results
suggest that in the rat kidney, Ach, like bradykinin, utilizes a
charybdotoxin-sensitive Ca++-activated K+
channel of intermediate conductance to elicit vasodilation and that
this effect may be dependent on cytochrome P450 activity.
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