Pulmonary vasoregulation by endothelin in conscious dogs after left lung transplantation.
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.
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Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Smedira
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Murray
P A
PA
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
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