Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation.
We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3-4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs.
Nishiwaki
K
K
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287.
Nyhan
D P
DP
Stuart
R S
RS
Rock
P
P
Desai
P M
PM
Peterson
W P
WP
Murray
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D001920:Bradykinin