ROLE OF K-HEART( CHANNELS IN THE VASODILATOR RESPONSE TO BRADYKININ IN THE RAT)

1 The role of K+ channels in the nitric oxide (NO)-independent coronar y vasodilator effect of bradykinin was examined in the Langendorff hea rt preparation in which nitroarginine was used to inhibit NO synthesis and elevate perfusion pressure; cyclo-oxygenase was inhibited with in domethacin. 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 expe rimental conditions adopted here. 3 The non-specific K+ channel inhibi tors, tetraethylammonium and procaine, reduced vasodilator responses t o bradykinin and cromakalim but not those to nitroprusside in the perf used heart treated with nitroarginine and indomethacin. 4 Glibenclamid e, an inhibitor of ATP-sensitive K+ channels. reduced vasodilator resp onses to cromakalim but did not affect those to bradykinin or nitropru sside. 5 Charybdotoxin, an antagonist of Ca2+-activated K+ channels, i nhibited responses to bradykinin but did not affect those to cromakali m or nitroprusside. 6 Nifedipine inhibited vasodilator responses to br adykinin and cromakalim without affecting those to nitroprusside. 7 In hibition of cytochrome P450 with clotrimazole reduced responses to bra dykinin but did not modify those to cromakalim or nitroprusside. 8 The se results suggest that bradykinin utilizes a Ca2+-activated K+ channe l to produce vasodilatation in the rat heart.