Influence of lemakalim on the pulmonary vascular bed of the cat.
Pulmonary vascular responses to the K+ATP channel opener, lemakalim, were investigated in the intact-chest cat under constant flow conditions. When tone in the pulmonary vascular bed was elevated, intralobar injections of lemakalim caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. Lemakalim was approximately 3-fold more potent than cromakalim in dilating the pulmonary vascular bed, and pulmonary vasodilator responses to these K+ATP channel openers were blocked by the K+ATP channel blocking agent, glybenclamide. Glybenclamide had no significant effect on pulmonary vasodilator responses to acetylcholine or vasoactive intestinal peptide (VIP) but decreased responses to calcitonin gene-related peptide (CGRP). These data show that lemakalim has potent pulmonary vasodilator activity and suggest that responses are due to activation of a glybenclamide-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
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002415:Cats; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D014660:Vasoactive Intestinal Peptide; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide