外源性血管紧张素-I对局部缺血范围的有害作用及其被卡托普利抑制的情况。

Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril.

作者信息

Rump A F, Rösen R, Korth A, Klaus W

机构信息

Institut für Pharmakologie, Universität Köln, Germany.

出版信息

Eur Heart J. 1993 Jan;14(1):106-12. doi: 10.1093/eurheartj/14.1.106.

DOI:10.1093/eurheartj/14.1.106

PMID:8432277

Abstract

The endogenous activity of the local renin-angiotensin system (RAS) and the anti-ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l-1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the reduction of the global coronary flow (CF) by exogenous angiotensin-I or angiotensin-II (EC50 = 10(-10) mol.l-1). It is concluded that the local RAS in isolated rabbit hearts is highly sensitive, whereas its endogenous activity is very low due to very low endogenous angiotensin-I content. Myocardial ischaemia (MI) was induced by the occlusion of a left coronary artery branch and MI was quantified from NADH surface fluorescence photography. MI was significantly enlarged (+35%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol.l-1). The reduction in CF and the increment in MI by angiotensin-I could be completely prevented by adding captopril at a low concentration (10(-6) mol.l-1) to the perfusion buffer. In the absence of exogenous angiotensin-I, captopril alone (10(-6) mol.l-1) neither significantly enhanced CF (P > 0.05), nor diminished MI (P > 0.05), supporting the finding of very low endogenous activity of the local RAS in this model. We, moreover, conclude that at a low concentration (10(-6) mol.l-1) captopril does not possess direct cardioprotective properties independent of its ACE inhibiting action.

摘要

在电驱动的兔Langendorff心脏（恒压：70 cmH₂O，台氏液，Ca²⁺ 1.8 mmol·L⁻¹）中研究了局部肾素-血管紧张素系统（RAS）的内源性活性以及卡托普利的抗缺血特性。累积浓度-反应曲线显示，外源性血管紧张素-I或血管紧张素-II对整体冠状动脉血流量（CF）的降低作用之间无显著差异（P>0.05）（EC₅₀ = 10⁻¹⁰ mol·L⁻¹）。得出的结论是，离体兔心脏中的局部RAS高度敏感，但其内源性活性非常低，原因是内源性血管紧张素-I含量极低。通过结扎左冠状动脉分支诱导心肌缺血（MI），并通过NADH表面荧光摄影对MI进行定量。外源性血管紧张素-I（6×10⁻⁹ mol·L⁻¹）可使MI显著扩大（+35%）（P<0.05）。在灌注缓冲液中加入低浓度（10⁻⁶ mol·L⁻¹）的卡托普利可完全防止血管紧张素-I引起的CF降低和MI增加。在没有外源性血管紧张素-I的情况下，单独使用卡托普利（10⁻⁶ mol·L⁻¹）既不会显著增加CF（P>0.05），也不会减少MI（P>0.05），这支持了该模型中局部RAS内源性活性非常低的发现。此外，我们得出结论，低浓度（10⁻⁶ mol·L⁻¹）的卡托普利不具有独立于其ACE抑制作用的直接心脏保护特性。