Effects of propofol and thiopental in isolated rat aorta and pulmonary artery

W. K. Park, C. Lynch, Roger A Johns

Research output: Contribution to journalArticle

Abstract

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(ω)-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 μM) and thiopental (10, 30, 100 μM) 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 μM propofol showed gradual and partial recovery over 15 min; 300 μM 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. These results suggest that propofol directly relaxes arterial smooth muscle, with subsequent progressive attenuation, possibly through the gradual inhibition of EDRF/NO production. Effects in the presence of indomethacin suggest that propofol and thiopental induce the release of vasodilating cyclooxygenase metabolites from vascular rings with intact endothelium.

Original languageEnglish (US)
Pages (from-to)956-963
Number of pages8
JournalAnesthesiology
Volume77
Issue number5
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Thiopental
Propofol
Pulmonary Artery
Aorta
Endothelium
Vasodilation
Indomethacin
Blood Vessels
Endothelium-Dependent Relaxing Factors
Thoracic Arteries
Phenylephrine
Prostaglandin-Endoperoxide Synthases
Vasoconstriction
Thoracic Aorta
Nitric Oxide Synthase
Smooth Muscle
Nitric Oxide
Thorax

Keywords

  • Anesthetics, intravenous: propofol; thiopental
  • Animals: rats
  • Arteries: aorta; pulmonary arteries
  • Endothelium: endothelium-derived relaxing factor
  • Pharmacology: indomethacin; N(ω)-nitro-L-arginine methyl ester; phenylephrine

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. / Park, W. K.; Lynch, C.; Johns, Roger A.

In: Anesthesiology, Vol. 77, No. 5, 1992, p. 956-963.

Research output: Contribution to journalArticle

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abstract = "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(ω)-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 μM) and thiopental (10, 30, 100 μM) 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 μM propofol showed gradual and partial recovery over 15 min; 300 μM 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{\circledR}) 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. These results suggest that propofol directly relaxes arterial smooth muscle, with subsequent progressive attenuation, possibly through the gradual inhibition of EDRF/NO production. Effects in the presence of indomethacin suggest that propofol and thiopental induce the release of vasodilating cyclooxygenase metabolites from vascular rings with intact endothelium.",
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