BACKGROUND: Infusion of propofol often causes significant vasodilation, which is followed by a profound drop in blood pressure. However, the exact underlying molecular mechanisms of this clinically important phenomenon remain unclear. OBJECTIVE: To determine the biological role of endothelium in propofol-induced vasorelaxation and the underlying molecular mechanisms of this response in the rat aorta. DESIGN, SETTING AND SUBJECTS: Ex vivo assessment of vasomotor function in rat aortic rings, with or without endothelium, after addition of propofol or etomidate. In vivo randomised study of haemodynamic changes in Sprague Dawley rats after administration of propofol, with or without prior infusion of a K(ATP) antagonist. In vitro measurement of intracellular calcium in cultured vascular smooth muscle cells (VSMC) treated with propofol. The experiments were conducted in a research laboratory at the National Cheng Kung University, Taiwan, from August 2008 to July 2009. INTERVENTIONS: Changes in isometric tension of precontracted rat aortic rings were recorded after cumulative addition of propofol (3-300µM). An ATP-sensitive potassium (K(ATP)) channel blocker, glibenclamide (10µM), was incubated in the organ bath before the addition of propofol. Haemodynamic changes after intravenous administration of propofol in the presence or absence of PNU-37883A (a vascular-specific K(ATP) channel blocker) were recorded in anaesthetised rats. Alterations in intracellular calcium and ATP levels in cultured VSMC treated with propofol were measured. RESULTS: Compared with etomidate, propofol induced a significant concentration-dependent vascular relaxation response that was independent of the presence of endothelium. The relaxation response was almost completely abolished by K(ATP) channel antagonism. Levels of intracellular calcium were significantly attenuated in cultured VSMC treated with propofol (10mM). Pre-treatment with PNU- 37883A significantly attenuated propofol-induced hypotension in anaesthetised rats. CONCLUSIONS: Development of hypotension after systemic administration of propofol is mainly caused by its direct relaxation effect on vascular smooth muscle. This response is mainly mediated by activation of K(ATP) channels.
BACKGROUND: Infusion of propofol often causes significant vasodilation, which is followed by a profound drop in blood pressure. However, the exact underlying molecular mechanisms of this clinically important phenomenon remain unclear. OBJECTIVE: To determine the biological role of endothelium in propofol-induced vasorelaxation and the underlying molecular mechanisms of this response in the rat aorta. DESIGN, SETTING AND SUBJECTS: Ex vivo assessment of vasomotor function in rat aortic rings, with or without endothelium, after addition of propofol or etomidate. In vivo randomised study of haemodynamic changes in Sprague Dawley rats after administration of propofol, with or without prior infusion of a K(ATP) antagonist. In vitro measurement of intracellular calcium in cultured vascular smooth muscle cells (VSMC) treated with propofol. The experiments were conducted in a research laboratory at the National Cheng Kung University, Taiwan, from August 2008 to July 2009. INTERVENTIONS: Changes in isometric tension of precontracted rat aortic rings were recorded after cumulative addition of propofol (3-300µM). An ATP-sensitive potassium (K(ATP)) channel blocker, glibenclamide (10µM), was incubated in the organ bath before the addition of propofol. Haemodynamic changes after intravenous administration of propofol in the presence or absence of PNU-37883A (a vascular-specific K(ATP) channel blocker) were recorded in anaesthetised rats. Alterations in intracellular calcium and ATP levels in cultured VSMC treated with propofol were measured. RESULTS: Compared with etomidate, propofol induced a significant concentration-dependent vascular relaxation response that was independent of the presence of endothelium. The relaxation response was almost completely abolished by K(ATP) channel antagonism. Levels of intracellular calcium were significantly attenuated in cultured VSMC treated with propofol (10mM). Pre-treatment with PNU- 37883A significantly attenuated propofol-induced hypotension in anaesthetised rats. CONCLUSIONS: Development of hypotension after systemic administration of propofol is mainly caused by its direct relaxation effect on vascular smooth muscle. This response is mainly mediated by activation of K(ATP) channels.
Authors: Andre Bredthauer; Angela Geiger; Michael Gruber; Sophie-Marie Pfaehler; Walter Petermichl; Diane Bitzinger; Thomas Metterlein; Timo Seyfried Journal: J Inflamm Res Date: 2021-08-11
Authors: Pritam Sinharoy; Ian N Bratz; Sayantani Sinha; Loral E Showalter; Spencer R Andrei; Derek S Damron Journal: PLoS One Date: 2017-06-23 Impact factor: 3.240