Pulmonary vasodilator responses to RP 52891 are mediated by activation of a glibenclamide-sensitive K+ATP channel.
Pulmonary vasodilator responses to the K+ATP channel opener, RP 52891, were investigated in the intact-chest cat under constant flow conditions. When pulmonary vascular tone was increased with U46619, intralobar injections of RP 52891 caused dose-related decreases in lobar arterial and systemic arterial pressures without altering left atrial pressure. RP 52891 was more potent than pinacidil but less potent than cromakalim in dilating the pulmonary vascular bed. Pulmonary vasodilator responses to RP 52891, cromakalim and pinacidil, but not to acetylcholine, nitroprusside or isoproterenol, were blocked by glibenclamide. These data demonstrate that RP 52891 has potent pulmonary vasodilator activity in the cat and suggest that responses are due to opening of a glibenclamide-sensitive K+ATP channel.
Hood
J S
JS
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
McMahon
T J
TJ
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010847:Picolines / Q000494:pharmacology*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D010847:Picolines; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011714:Pyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; C061043:aprikalim; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020110:Pinacidil; D000255:Adenosine Triphosphate; D007545:Isoproterenol; D000109:Acetylcholine; D005905:Glyburide