Pulmonary vascular alpha 1-adrenoreceptor activity in conscious dogs after left lung autotransplantation.
We investigated the extent to which sympathetic alpha 1-adrenoreceptor activation is involved in chronic pulmonary vascular regulation in conscious dogs after left lung autotransplantation (LLA). Continuous left pulmonary vascular pressure-flow plots were generated in conscious dogs 3-4 wk post-LLA and in identically instrumented conscious dogs not subjected to LLA (sham-operated controls). LLA resulted in a marked upward shift in the baseline left pulmonary vascular pressure-flow relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The sympathetic alpha 1-adrenoreceptor antagonist prazosin partially reversed (P < 0.01) the LLA-induced increase in pulmonary vascular resistance. Circulating concentrations of norepinephrine and epinephrine at 2 and 4 wk post-LLA were not significantly different from values measured in control dogs. However, the dose-response relationship to the exogenous administration of the sympathetic alpha 1-adrenoreceptor agonist phenylephrine was shifted (P < 0.05) to the left post-LLA compared with control, which indicates an increase in pulmonary vascular reactivity to alpha 1-adrenoreceptor activation. This effect was not due to a generalized increase in pulmonary vascular reactivity to vasoconstrictor stimuli because the dose-response relationship to the thromboxane analogue U-46619 was not significantly altered post-LLA compared with control. Thus LLA results in a chronic increase in pulmonary vascular resistance in conscious dogs. A component of the increase in pulmonary vascular resistance resulting from LLA is mediated by an enhanced reactivity to sympathetic alpha 1-adrenoreceptor activation.
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287.
K
K
Nishiwaki
D P
DP
Nyhan
R S
RS
Stuart
P M
PM
Desai
W P
WP
Peterson
P
P
Rock
C G
CG
Pribble
P A
PA
Murray
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014182:Transplantation, Autologous; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002395:Catecholamines; D011450:Prostaglandin Endoperoxides, Synthetic; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine