CONTRIBUTION OF CALCIUM-ACTIVATED POTASSIUM CHANNELS TO THE VASODILATOR EFFECT OF BRADYKININ IN THE ISOLATED, PERFUSED KIDNEY OF THE RAT

1 NO- and prostaglandin-independent, endothelium-dependent vasodilator responses to bradykinin are attributed to release of a hyperpolarizin g factor. Therefore, the contribution of K+ channels to the renal vaso dilator effect of bradykinin was examined in rat perfused kidneys that were preconstricted with phenylephrine and treated with N-G-nitro-L-a rginine (L-NOARG) and indomethacin to inhibit NO and prostaglandin syn thesis. 2 The non-specific K+ channel inhibitors, TEA and TBA reduced vasodilator responses to bradykinin and cromakalim but not those to ni troprusside. 3 Glibenclamide. an inhibitor of ATP-sensitive K+ channel s, blocked the vasodilator response to cromakalim without affecting re sponses to bradykinin. 4 Charybdotoxin, a selective inhibitor of Ca2+- activated K+ channels, greatly attenuated vasodilator responses to bra dykinin without affecting those to cromakalim or nitroprusside. 5 Iber iotoxin and leiurotoxin, inhibitors of large and small conductance Ca2 +-activated K+ channels, respectively, were without effect on vasodila tor responses to bradykinin, cromakalim or nitroprusside. 6 These resu lts implicate K+ channels, specifically Ca2+-activated K+ channels of intermediate conductance, in the renal vasodilator effect of bradykini n and, thereby, support a role for a hyperpolarizing factor.