Mechanisms responsible for renoprotective effects of renin-angiotensin inhibitors

In recent years, the focus of interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of hypertension and organ injury has changed to a major emphasis on the role of the local RAS in specific tissues. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by independent multiple mechanisms. Ang II is compartmentalized in the renal interstitial fluid and the proximal tubular compartments with much higher concentrations than those existing in the circulation. It has also been revealed that inappropriate activation of the intrarenal RAS is an important contributor to the pathogenesis of chronic kidney disease (CKD). Indeed, most national guideline groups now recommend the use of RAS inhibitors in preference to other antihypertensive agents for hypertensive patients with CKD. In this review, we will briefly summarize our current understanding of independent regulation of the intrarenal RAS. We will also discuss the impact of RAS inhibitors in preventing the progressive increases in the intrarenal RAS during the development of CKD.