Cumming A D, Nimmo G R, Craig K J, McGilchrist A, Hayes P C
University Department of Medicine, Royal Infirmary, Edinburgh, UK.
Agents Actions Suppl. 1992;38 ( Pt 2):211-8.
The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function.
a）实验性感染性休克，以及b）肝硬化腹水患者，因为在这两种情况下，血浆激肽释放酶-激肽系统的激活都与病理性全身血管舒张有关，这可能引发反射性神经内分泌激活和肾溶质潴留。在实验性脓毒症早期给予抑肽酶，可维持动脉血压、全身血管阻力（SVR）、肌酐清除率和钠排泄，而这些指标在对照组中均下降。抑肽酶还可阻止肺动脉压和血浆肾素活性（PRA）升高。在脓毒症晚期给予抑肽酶，可使动脉血压和SVR迅速升至基线水平。在肝硬化患者中，抑肽酶可使基线值较低的患者的SVR升高，并改善所有受试者的肾小球滤过率、肾血浆流量和钠排泄；PRA被抑肽酶抑制。抑肽酶可逆转这两种情况下的病理性全身血管舒张，这与肾素释放减少和肾功能改善有关。
