Pulmonary vascular beta-adrenoreceptor activity in conscious dogs after left lung autotransplantation.
Our objective was to determine whether chronic denervation associated with left lung autotransplantation (LLA) results in an alteration in sympathetic beta-adrenoreceptor regulation of the pulmonary circulation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 2-4 wk post-LLA and in sham-operated control conscious dogs. We tested the hypothesis that endogenous sympathetic beta-adrenoreceptor activation via circulating catecholamines acted to attenuate the chronic increase in pulmonary vascular resistance post-LLA. Administration of the sympathetic beta-adrenoreceptor antagonist propranolol had no significant effect on the LPQ relationship post-LLA. We also tested the hypothesis that pulmonary vascular reactivity to sympathetic beta-adrenoreceptor activation would be increased post-LLA. The thromboxane analogue U-46619 was used to acutely preconstrict (P < 0.01) the pulmonary circulation in control dogs; this preconstriction shifted the LPQ relationship to the same position measured post-LLA. Under these conditions, cumulative doses of the beta-adrenoreceptor agonist isoproterenol caused pulmonary vasodilation (P < 0.01) in the control group but had no effect post-LLA. However, after acute preconstriction with U-46619, the pulmonary vasodilator response (P < 0.01) to isoproterenol post-LLA was not significantly different from that in the control group. These differential responses to isoproterenol with and without acute preconstriction indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is mediated by passive nonvasoactive mechanisms. Moreover, sympathetic beta-adrenoreceptor reactivity of the pulmonary circulation is not enhanced by chronic denervation resulting from the LLA procedure.
Nishiwaki
K
K
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4961.
Rock
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P
Stuart
R S
RS
Nyhan
D P
DP
Peterson
W P
WP
Murray
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003714:Denervation; D004285:Dogs; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014182:Transplantation, Autologous; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D011450:Prostaglandin Endoperoxides, Synthetic; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007545:Isoproterenol