The importance of the intrarenal renin-angiotensin system.

Evidence suggests that virtually every organ system in the human body possesses a local renin-angiotensin system (RAS). These local systems seem to be independently regulated and compartmentalized from the plasma circulation, perhaps with the exception of the vascular endothelial system, which is responsible for maintaining physiological plasma levels of RAS components. Among these local RASs, the kidney RAS--the focus of this Review--seems to be of critical importance for the regulation of blood pressure and salt balance. Indeed, overactivation of the intrarenal RAS in certain disease states constitutes a pathogenic mechanism that leads to tissue injury, proliferation, fibrosis and ultimately, end-organ damage. Intrarenal levels of angiotensin peptides are considerably higher than those in plasma or any other organ tissue. Moreover, the kidney has a unique capacity to degrade angiotensin peptides, perhaps to maintain its intrinsic homeostasis. Interestingly, each local RAS has a distinct enzymatic profile resulting in different patterns of angiotensin fragment generation in different tissues. A better understanding of the autocrine and paracrine mechanisms involved in the renal RAS and other local RASs might direct future organ-specific therapy.