Helmy Ahmed, Ferguson James W, Hayes Peter C, Newby David E, Webb David J
Department of Hepatology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.
J Cardiovasc Pharmacol. 2006 Apr;47(4):556-60. doi: 10.1097/01.fjc.0000211727.23304.49.
Bradykinin is an endothelium-dependent vasodilator and inflammatory mediator. The aim of the present study was to examine the effects of bradykinin on peripheral vascular tone in patients with cirrhosis and ascites. Forearm blood flow was measured using venous occlusion plethysmography in 8 patients with biopsy-proven alcohol-induced cirrhosis, ascites, and portal hypertension, and 8 age- and sex-matched healthy controls. On 1 occasion, subjects received an intrabrachial infusion of the selective bradykinin antagonist B9340 (1.5-13.5 nmol/min) followed by a control vasoconstrictor norepinephrine (60-540 pmol/min), and on another occasion bradykinin (100-900 pmol/min) followed by the endothelium-independent vasodilator, sodium nitroprusside (SNP, 2-8 microg/min). Bradykinin and SNP caused a dose-dependent vasodilatation (P < 0.001 for both) that did not differ between the 2 groups. Although norepinephrine caused a similar dose-dependent vasoconstriction in both groups (P < 0.001), B9340 had no effect on forearm blood flow in either group (at 13.5 nmol/min in patients; -5%, 95% CI -13-3). Bradykinin does not provide a major contribution to the maintenance of peripheral vascular tone in patients with cirrhosis and ascites. Our findings also suggest that, in contrast to cardiovascular disease, patients with liver cirrhosis do not have marked endothelial dysfunction.
缓激肽是一种内皮依赖性血管舒张剂和炎症介质。本研究的目的是检测缓激肽对肝硬化腹水患者外周血管张力的影响。采用静脉阻断体积描记法测量了8例经活检证实为酒精性肝硬化、腹水和门静脉高压患者以及8例年龄和性别匹配的健康对照者的前臂血流量。在一次实验中,受试者接受肱动脉内输注选择性缓激肽拮抗剂B9340(1.5 - 13.5 nmol/min),随后输注对照血管收缩剂去甲肾上腺素(60 - 540 pmol/min);在另一次实验中,先输注缓激肽(100 - 900 pmol/min),随后输注非内皮依赖性血管舒张剂硝普钠(SNP,2 - 8 μg/min)。缓激肽和硝普钠均引起剂量依赖性血管舒张(两者P均<0.001),两组间无差异。虽然去甲肾上腺素在两组中均引起相似的剂量依赖性血管收缩(P<0.001),但B9340对两组的前臂血流量均无影响(患者组13.5 nmol/min时;-5%,95%CI -13 - 3)。缓激肽对肝硬化腹水患者外周血管张力的维持作用不大。我们的研究结果还表明,与心血管疾病不同,肝硬化患者没有明显的内皮功能障碍。