title: Pulmonary vasoregulation by endothelin in conscious dogs after left lung transplantation.
abstract: We tested the hypothesis that regulation of the pulmonary circulation by endogenous endothelin (ET) during normoxia and hypoxia was altered in conscious dogs 1 mo after left lung autotransplantation (LLA). Sham-operated control and post-LLA dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LP-Q) relationship. LP-Q plots were generated on separate days during normoxia and hypoxia (arterial PO(2) approximately 50 Torr) in the intact condition, after selective ET(A)-receptor inhibition (BQ-485), and after combined ET(A+B)-receptor inhibition (bosentan). Although LLA resulted in a chronic increase in pulmonary vascular resistance, the ET-receptor antagonists had no effect on the LP-Q relationship during normoxia in either group. The magnitude of hypoxic pulmonary vasoconstriction (HPV) was flow dependent in both groups, and the HPV response was potentiated post-LLA compared with control. ET(A)-receptor inhibition attenuated the HPV response to the same extent in both groups. ET(A+B)-receptor inhibition attenuated the HPV response to a greater extent than did ET(A)-receptor inhibition alone, and this effect was greater post-LLA compared with control. Plasma ET-1 concentration only increased during hypoxia in the LLA group. These results indicate that ET does not regulate the baseline LP-Q relationship in either group. Both ET(A)- and ET(B)-receptor activation mediate a component of HPV in conscious dogs, and the vasoconstrictor influence of ET(B)-receptor activation is enhanced post-LLA.
authors.affiliation: Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Doi
authors.forename: N
authors.initials: N
authors.lastname: Smedira
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000077300:Bosentan; D002245:Carbon Dioxide / Q000097:blood; D003243:Consciousness; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D017466:Receptors, Endothelin / Q000378:metabolism; D012119:Respiration; D013449:Sulfonamides / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D017466:Receptors, Endothelin; D013449:Sulfonamides; C083116:BQ 485; D002245:Carbon Dioxide; D000077300:Bosentan; D010100:Oxygen