The Mechanisms of Propofol-Induced Vascular Relaxation and Modulation by Perivascular Adipose Tissue and Endothelium

Abstract

Propofol causes hypotension due to relaxation of vascular smooth muscle cells through its direct or indirect vasodilator effects. Perivascular adipose tissue (PVAT) and endothelium attenuate vascular contraction, and the function of PVAT is altered in hypertension and diabetes. Whether PVAT affects the action of anesthetics on vascular function is unknown. We studied the mechanisms of propofol-induced relaxation in relation to the involvement of PVAT and endothelium. Thoracic aortic rings from Wistar rats were prepared with or without PVAT (PVAT+ and PVAT-), intact endothelium (E+), or both, or with the endothelium removed (E-) for functional studies. In phenylephrine precontracted vessels, propofol-induced relaxation was highest with both PVAT and E+ and lowest in vessels denuded of both PVAT and endothelium. Propofol-induced relaxation occurred via both endothelium-dependent and -independent mechanisms. The relaxation response induced by propofol was significantly reduced by nitric oxide synthase inhibitor (l-NNA), K(+) channel blockers (tetraethylammonium and glibenclamide) in E+ and E- vessels, and by soluble guanylyl cyclase inhibitor 1H-(1,2,4) oxadiazolo (4,3-A) quinazoline-1-one and hydrogen peroxide scavenger (catalase) in E- vessels. The presence of PVAT significantly enhanced the relaxation response induced by propofol. In contrast to phenylephrine precontracted vessels in which the presence of PVAT or endothelium had an effect, in vessels precontracted with KCl, propofol-induced relaxation was similar among the 4 types of vessel preparation. PVAT enhances the relaxation effect induced by propofol in rat aorta through both endothelium-dependent and endothelium-independent pathways thus highlighting the clinical importance of PVAT.