Prevention, protection, and the intrarenal renin-angiotensin systems.
Prevention, protection, and the intrarenal renin-angiotensin systems.
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DOI：
10.1053/snep.2001.26806
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发表时间：
2001-11
影响因子：
3.3
通讯作者：
D. Warnock
中科院分区：
文献类型：
--
作者：
D. Warnock
血管紧张素转换酶（ACE）抑制剂、血管紧张素受体拮抗剂或醛固酮拮抗剂的使用对肾小球和间质纤维化相关肾病的进展具有重要的有益作用，尤其是如果不良副作用（如高钾血症）可以最小化。因为慢性肾功能不全和蛋白尿很可能是心血管危险因素，令人兴奋的是，最近的大规模流行病学研究（心脏结局和预防评估[HOPE]）显示了ACE抑制剂的心脏保护和肾脏保护作用。似乎矛盾的是，这种肾保护作用在血浆肾素活性可能受到抑制的糖尿病中是明显的。即使在这种情况下，似乎也存在肾血管紧张素系统的激活，并且这些肾内系统的抑制与这些药物的肾保护作用有关。最近的研究已经确定了几乎所有在肾腔室中产生血管紧张素II所需的成分，并表明可能通过AT（1）受体对远端肾单位中的NaCl转运产生直接影响。这种管腔内的肾素-血管紧张素系统的成分可能会受到饮食中盐摄入量变化的剧烈调节，这为更好地理解盐平衡的正常维持提供了机会。ACE抑制剂和血管紧张素受体拮抗剂的肾保护作用是否涉及这些途径的抑制是一个需要解决的重要问题。
The use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, or aldosterone antagonists can have important beneficial effects on the progression of renal disease associated with glomerular and interstitial fibrosis, especially if the adverse side effects (eg, hyperkalemia) can be minimized. Because it appears that chronic renal insufficiency and proteinuria may well be cardiovascular risk factors, it is exciting to note that recent large scale epidemiologic studies (Heart Outcomes and Prevention Evaluation [HOPE]) have shown both cardioprotective and renoprotective effects of ACE inhibition. It appears paradoxic that such renoprotective effects are clearly evident in diabetes mellitus in which the plasma renin activity may be suppressed. Even in this setting, it appears that there is activation of the renal angiotensin system(s), and inhibitions of these intrarenal systems are involved in the renoprotective effects of these agents. Recent studies have identified nearly all of the components needed to generate angiotensin II in the renal luminal compartment, and suggest that there may be a direct effect through AT(1) receptors on NaCl transport in the distal nephron. The possibility that the components of this intraluminal renin-angiotensin system may be acutely regulated by variations in dietary salt intake provides an opportunity to better understand the normal maintenance of salt balance. Whether or not inhibition of these pathways is involved in the renoprotective effects of ACE inhibitors and angiotensin receptor antagonists is an important issue to be addressed.