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 hyperpolarizing factor. Therefore, the contribution of K+ channels to the renal vasodilator effect of bradykinin was examined in rat perfused kidneys that were preconstricted with phenylephrine and treated with NG-nitro-L-arginine (L-NOARG) and indomethacin to inhibit NO and prostaglandin synthesis. 2. The non-specific K+ channel inhibitors, TEA and TBA reduced vasodilator responses to bradykinin and cromakalim but not those to nitroprusside. 3. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, blocked the vasodilator response to cromakalim without affecting responses to bradykinin. 4. Charybdotoxin, a selective inhibitor of Ca(2+)-activated K+ channels, greatly attenuated vasodilator responses to bradykinin without affecting those to cromakalim or nitroprusside. 5. Iberiotoxin and leiurotoxin, inhibitors of large and small conductance Ca(2+)-activated K+ channels, respectively, were without effect on vasodilator responses to bradykinin, cromakalim or nitroprusside. 6. These results implicate K+ channels, specifically Ca(2+)-activated K+ channels of intermediate conductance, in the renal vasodilator effect of bradykinin and, thereby, support a role for a hyperpolarizing factor.