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.
Rapacon
M
M
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Mieyal
P
P
McGiff
J C
JC
Fulton
D
D
Quilley
J
J
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011448:Prostaglandin Antagonists; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium