Hollenberg N K
Am J Med. 1984 May 31;76(5B):22-8. doi: 10.1016/0002-9343(84)90879-9.
Among vascular beds, that of the kidney is especially responsive to angiotensin II, perhaps a reflection of the fact that the renin-angiotensin axis is normally a volume-control rather than a pressure-control system. The dose of angiotensin required to induce renal vasoconstriction in a normal subject receiving a typical, liberal sodium intake, for example, is about an order of magnitude lower than that required to induce a pressor response. Indeed, compelling arguments can be made for a local, intrarenal role as angiotensin's first action in phylogeny, with additional cardiovascular and endocrine responses arising later. In patients with essential hypertension, in whom renal vascular tone is commonly increased, converting enzyme inhibitors such as teprotide and captopril induce a potentiated acute renal vascular response: renal blood flow increases more than it does in normal subjects. The result is a consistent, early increase in sodium excretion and an occasional increase in glomerular filtration rate. Reduced aldosterone release consequent to the block of angiotensin II formation also contributes to the natriuresis and results in positive potassium balance. With long-term therapy, renal function tends to be very well maintained. In renal artery stenosis the situation is more complex: as perfusion pressure distal to the stenosis falls, typically afferent arteriolar dilatation exists and glomerular capillary pressure tends to be maintained by an increase in postglomerular resistance. To the extent that this increase is angiotensin-mediated, suppression of angiotensin formation with captopril can reduce glomerular capillary pressure and thus filtration rate. This is well tolerated in the patient with unilateral stenosis and a healthy contralateral kidney, but can provoke renal failure when the stenosis is bilateral or involves a solitary kidney. The available evidence suggests that the converting enzyme inhibitor's influence on the kidney primarily reflects reduced angiotensin II formation, although reduced kinin degradation or increased prostaglandin synthesis may also have an influence. Whatever the mechanism responsible for the renal response, there are compelling reasons for suspecting that the salutary action of captopril on the kidney makes a substantial contribution to its over-all efficacy in the treatment of hypertension.
在各种血管床中，肾脏血管床对血管紧张素II尤为敏感，这或许反映了肾素 - 血管紧张素轴通常是一个容量控制系统而非压力控制系统这一事实。例如，在正常受试者摄入典型的大量钠时，诱导肾血管收缩所需的血管紧张素剂量比诱导升压反应所需的剂量低约一个数量级。实际上，有充分的理由认为，在系统发育过程中，血管紧张素的首要作用是在肾脏局部发挥的，随后才出现额外的心血管和内分泌反应。在原发性高血压患者中，肾血管张力通常会增加，替普罗肽和卡托普利等转换酶抑制剂会诱导增强的急性肾血管反应：肾血流量的增加幅度大于正常受试者。结果是钠排泄持续早期增加，肾小球滤过率偶尔也会增加。由于血管紧张素II生成受阻导致醛固酮释放减少，这也有助于利钠作用，并导致钾平衡为正。长期治疗时，肾功能往往能得到很好的维持。在肾动脉狭窄时情况更为复杂：随着狭窄远端的灌注压力下降，通常会出现入球小动脉扩张，肾小球毛细血管压力往往通过肾小球后阻力增加得以维持。在这种增加是由血管紧张素介导的程度上，用卡托普利抑制血管紧张素生成可降低肾小球毛细血管压力，从而降低滤过率。这在单侧狭窄且对侧肾脏健康的患者中耐受性良好，但当狭窄是双侧的或累及孤立肾时，可能会引发肾衰竭。现有证据表明，转换酶抑制剂对肾脏的影响主要反映为血管紧张素II生成减少，尽管激肽降解减少或前列腺素合成增加也可能有影响。无论导致肾脏反应的机制如何，都有充分理由怀疑卡托普利对肾脏的有益作用对其治疗高血压的总体疗效有重大贡献。
