Role of K+ channels in the vasodilator response to bradykinin in the rat heart.
1. The role of K+ channels in the nitric oxide (NO)-independent coronary vasodilator effect of bradykinin was examined in the Langendorff heart preparation in which nitroarginine was used to inhibit NO synthesis and elevate perfusion pressure; cyclo-oxygenase was inhibited with indomethacin. 2. The K+ channel inhibitors, tetraethylammonium, procaine and charybdotoxin, but not glibenclamide, further increased perfusion pressure suggesting a role for K+ channels, other than ATP-sensitive K+ channels, in the regulation of coronary vascular tone under the experimental conditions adopted here. 3. The non-specific K+ channel inhibitors, tetraethylammonium and procaine, reduced vasodilator responses to bradykinin and cromakalim but not those to nitroprusside in the perfused heart treated with nitroarginine and indomethacin. 4. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, reduced vasodilator responses to cromakalim but did not affect those to bradykinin or nitroprusside. 5. Charybdotoxin, an antagonist of Ca(2+)-activated K+ channels, inhibited responses to bradykinin but did not affect those to cromakalim or nitroprusside. 6. Nifedipine inhibited vasodilator responses to bradykinin and cromakalim without affecting those to nitroprusside. 7. Inhibition of cytochrome P450 with clotrimazole reduced responses to bradykinin but did not modify those to cromakalim or nitroprusside. 8. These results suggest that bradykinin utilizes a Ca(2+)-activated K+ channel to produce vasodilatation in the rat heart.
Fulton
D
D
Department of Pharmacology, New York Medical College, Valhalla 10595.
McGiff
J C
JC
Quilley
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D015220:Calcium Channels; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D019335:Nitroarginine; D011343:Procaine; D001120:Arginine; D001920:Bradykinin; D007213:Indomethacin