Effects of propofol and thiopental in isolated rat aorta and pulmonary artery.
This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega-nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium-denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS)
Park
W K
WK
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Lynch
C
C
Johns
R A
RA
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D015742:Propofol / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013874:Thiopental / Q000494:pharmacology*
D001120:Arginine; D013874:Thiopental; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D015742:Propofol