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.
Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, OH 44195, USA.
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Kondo
S O
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Kim
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Murray
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