Femoral vasodilation to cromakalim is blocked by U37883A, a non-sulphonylurea that selectively inhibits KATP channels.
The purpose of the present study was to determine the effects of U37883A, a non-sulphonylurea inhibitor of KATP channels, in the femoral vascular bed of the anaesthetized dog. Administration of U37883A, 4-morpholinecarboxamidine-N-1-adamentyl-N"-cyclohexyl hydrochloride (2.5 mg kg-1, i.v.), significantly inhibited the femoral vasodilator response to intra-femoral arterial injection of cromakalim, an activator of KATP channels. In contrast, U37883A had no effect on the femoral vasodilator responses to nitroglycerin, isoprenaline, 5-HT, or 5-carboxamidotryptamine, suggesting this agent is a novel and selective inhibitor of hindlimb vasodilation induced by KATP-channel activation. Since U37883A did not significantly alter baseline femoral blood flow and femoral vascular resistance, the present data suggest that KATP channels do not contribute, in large measure, to regulating the canine femoral vascular bed under resting conditions in-vivo.
Lippton
H
H
Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Choe
E
E
Franklin
E
E
Grivas
T
T
Flint
L
L
Hyman
A
A
Ferrara
J
J
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D004347:Drug Interactions; D005269:Femur / Q000098:blood supply / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D001578:Benzopyrans; D009025:Morpholines; D015221:Potassium Channels; D011758:Pyrroles; D017366:Serotonin Receptor Agonists; D014665:Vasodilator Agents; D019806:Cromakalim; D012701:Serotonin; C082658:U 37883A; C047087:5-carboxamidotryptamine; D005996:Nitroglycerin; D007545:Isoproterenol; D000218:Adamantane