The endothelin ETB receptor antagonist BQ-788 reduces the pulmonary vasodilator effect of endothelin-1 during acute hypoxia in pigs.
Pigs were subjected to acute, intermittent hypoxia (fraction of inhaled O2 0.1, n = 10). The increase in mean pulmonary artery pressure during hypoxia was not altered after i.v. administration of the selective endothelin ETB receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1- methoxycarbonyltryptophanyl-D-norleucine) (1 mg). However, the vasodilatory effect of endothelin-1 (25 ng/kg per min) infused into the pulmonary artery during hypoxia was attenuated by BQ-788. The present results suggest that the pulmonary vasodilator effect of exogenously administered endothelin-1 during acute hypoxia is mediated by endothelin ETB receptors in the pig. Furthermore, endothelin ETB receptor antagonism with BQ-788 does not influence the pulmonary vascular response to acute hypoxia.
Holm
P
P
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Liska
J
J
Franco-Cereceda
A
A
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D044023:Receptor, Endothelin B; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044023:Receptor, Endothelin B; C086539:BQ 788