巴比妥类药物抑制由环鸟苷酸介导的内皮依赖性和非内皮依赖性舒张。

Barbiturates inhibit endothelium-dependent and independent relaxations mediated by cyclic GMP.

作者信息

Terasako K, Nakamura K, Toda H, Kakuyama M, Hatano Y, Mori K

机构信息

Department of Anesthesia, Kyoto University Hospital, Japan.

出版信息

Anesth Analg. 1994 May;78(5):823-30. doi: 10.1213/00000539-199405000-00001.

DOI:10.1213/00000539-199405000-00001

PMID:8160977

Abstract

The inhibitory effects of volatile and local, but not intravenous, anesthetics on endothelium-dependent relaxations of blood vessels have been demonstrated in vitro by several investigators. The aim of this study was to determine the effects of barbiturates on endothelium-dependent arterial relaxation and elucidate the mechanism(s) responsible. Canine mesenteric arteries and rat aortae were isolated, and tension changes in helical strips were recorded. Endothelium-dependent relaxations elicited by acetylcholine and bradykinin in canine mesenteric arteries, and those by acetylcholine in rat aortae, were significantly attenuated by thiopental (3 x 10(-4) M) pretreatment. Sodium nitroprusside (SNP)-induced, endothelium-independent relaxations were significantly attenuated by thiopental (10(-4)-3 x 10(-4) M). The effects of pentobarbital were less marked than those of thiopental. Acetylcholine (10(-5) M)-stimulated levels of 3',5'-cyclic guanosine monophosphate (cGMP) in rat aortae were reduced significantly by thiopental and pentobarbital (both 10(-3) M), and SNP (3 x 10(-7) M)-stimulated levels were reduced by thiopental (3 x 10(-4)-10(-3) M) and pentobarbital (10(-3) M). We conclude that barbiturates inhibit cGMP-mediated endothelium-dependent and independent arterial relaxations. Inhibition of endothelium-dependent relaxation by barbiturates may be mediated by their effects on vascular smooth muscle itself and not on endothelium.

摘要

几位研究者已在体外证实挥发性麻醉药和局部麻醉药而非静脉麻醉药对血管内皮依赖性舒张有抑制作用。本研究旨在确定巴比妥类药物对内皮依赖性动脉舒张的影响并阐明其作用机制。分离犬肠系膜动脉和大鼠主动脉，记录螺旋条带的张力变化。硫喷妥钠（3×10⁻⁴ M）预处理可显著减弱乙酰胆碱和缓激肽引起的犬肠系膜动脉内皮依赖性舒张以及乙酰胆碱引起的大鼠主动脉内皮依赖性舒张。硝普钠（SNP）诱导的非内皮依赖性舒张在硫喷妥钠（10⁻⁴ - 3×10⁻⁴ M）作用下显著减弱。戊巴比妥的作用不如硫喷妥钠明显。硫喷妥钠和戊巴比妥（均为10⁻³ M）可显著降低乙酰胆碱（10⁻⁵ M）刺激的大鼠主动脉中3',5'-环磷酸鸟苷（cGMP）水平，硫喷妥钠（3×10⁻⁴ - 10⁻³ M）和戊巴比妥（10⁻³ M）可降低SNP（3×10⁻⁷ M）刺激的cGMP水平。我们得出结论，巴比妥类药物抑制cGMP介导的内皮依赖性和非内皮依赖性动脉舒张。巴比妥类药物对内皮依赖性舒张的抑制可能是通过其对血管平滑肌本身而非内皮的作用介导的。