Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs.
BACKGROUND
The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state.


METHODS
Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators.


RESULTS
Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation.


CONCLUSIONS
These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.
Kondo
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Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, OH 44195, USA.
Kim
S O
SO
Murray
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016292:Procedural Sedation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D001920:Bradykinin; D015742:Propofol