Inhibitory effect of propofol on endothelium-dependent relaxation and blood pressure lowering in rats

Kim, Shang-Jin; Kim, Jeong-gon; Joe, Sung-gun; Kang, Hyung-sub; Kim, Jin-shang

Korean Journal of Veterinary Research 2004;44(3):357-366.

Shang-Jin Kim, Jeong-gon Kim, Sung-gun Joe, Hyung-sub Kang, Jin-shang Kim

Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University

흰쥐에서 혈관내피 의존적인 혈관이완과 혈압하강에 대한 propofol의 억제 효과

김상진, 김정곤, 조성건, 강형섭, 김진상

전북대학교 생체안전성연구소

Abstract

We studied the effect of propofol (PPF) on the endothelium-dependent vascular responses in isolated rat thoracic aorta. In aortic rings with endothelium, PPF inhibited the phenylephrine (PE)-induced contraction in a concentration-dependent manner. In PE-precontracted preparations, PPF attenuated the endothelium-dependent relaxation by acetylcholine but not by A23187. And PPF did not attenuate the endothelium-independent relaxation by sodium nitroprusside (SNP). The relaxation induced by acetylcholine in PE-precontracted aortic rings was significantly augmented by zaprinast, a cGMP-specific phosphodiesterase inhibitor, and this augmentation was inhibited by PPF. Although SNP-induced relaxation was significantly augmented by zaprinast, this augmentation was not inhibited by PPF. In preparations preconstricted with PE, the PPF-induced relaxation was inhibited by atropine. In addition, PPF attenuated the vasorelaxation by phosphodiesterase inhibitors (IBMX, Ro20-1724 or zaprinast except milrinone). In vivo, the infusion of acetylcholine and SNP showed decreased arterial blood pressure in rats. The pre-injection of PPF inhibited the acetylcholine-induced blood pressure lowering, but not the SNP-induced blood pressure lowering. These results suggest that PPF can attenuate in part the acetylcholine-induced vasorelaxation and blood pressure lowering through the inhibition of the acetylcholine receptor-mediated endothelium-derived relaxing factor by acting on endothelium. It is considered that the inhibitory effect of PPF on the vasorelaxation is due to the decreased level of cGMP which can be attributed to the inhibition of the muscarinic receptor and/or receptor-G-protein interaction.

Key Words: propofol, cGMP, endothelium, vasorelaxation, rat aorta