title: The pulmonary vascular response to propofol in the isolated perfused rat lung.
abstract: This study investigated the effect of propofol on the pulmonary vascular bed of the rat. Propofol (5 x 10(-6) to 5 x 10(-4) M) did not alter the basal perfusion pressure in isolated rat lungs perfused at a constant flow (0.03 mL g body wt-1 min-1) with Krebs-Henseleit solution. When perfusion pressure was elevated by raising the K+ concentration to 30 mM (depolarizing Krebs-Henseleit solution), propofol decreased it in a concentration-dependent manner. Indomethacin (3 x 10(-6) M) and NG-nitro-L-arginine methyl ester (10(-4) M) did not affect the response to propofol, which excluded the role of cyclo-oxygenase metabolites and nitric oxide, respectively. The ATP-sensitive K+ (K+ATP) channel blocker glibenclamide (3 x 10(-6) and 10(-5) M) inhibited the vasodilator effect of propofol. When lungs were perfused with Ca(2+)-free depolarizing Krebs-Henseleit solution, 0.1-2.5 mM Ca+2 produced a concentration-dependent pressor response. Propofol (5 x 10(-5) M) attenuated the vasopressor response to Ca2+ significantly. In conclusion, the activation of K+ATP channels is probably the major mechanism of the vasodilator effect of propofol, at clinically relevant concentrations, in the rat lung. The Ca2+ antagonistic property of propofol is evident only at higher concentrations.
authors.affiliation: Department of Anesthesiology, Turkiye Yuksek Ihtisas Hastanesi, Ankara, Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Erdemli
authors.forename: B C
authors.initials: BC
authors.lastname: Tel
authors.forename: B
authors.initials: B
authors.lastname: Gumusel
authors.forename: I
authors.initials: I
authors.lastname: Sahin-Erdemli
mesh_terms: D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011188:Potassium / Q000097:blood; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D015742:Propofol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018686:Anesthetics, Intravenous; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001120:Arginine; D019001:Nitric Oxide Synthase; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D015742:Propofol