Independent regulation of renin-angiotensin-aldosterone system in the kidney

Abstract

Renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating renal hemodynamics and functions, as well as in the pathophysiology of hypertension and renal disease. In the kidney, angiotensin II (Ang II) production is controlled by independent multiple mechanisms. Ang II is compartmentalized in the renal interstitial fluid with much higher concentrations than those existing in the circulation. Inappropriate activation of the intrarenal RAAS is an important contributor to the pathogenesis of hypertension and renal injury. It has been revealed that intrarenal Ang II levels are predominantly regulated by angiotensinogen and therefore, urinary angiotensinogen could be a biomarker for intrarenal Ang II generation. In addition, recent studies have demonstrated that aldosterone contributes to the progression of renal injury via direct actions on glomerular podocytes, mesangial cells, proximal tubular cells and tubulo-interstitial fibroblasts through the activation of locally expressed mineralocorticoid receptor. Thus, it now appears that intrarenal RAAS is independently regulated and its inappropriate activation contributes to the pathogenesis of the development of hypertension and renal disease. This short review article will focus on the independent regulation of the intrarenal RAAS with an emphasis on the specific role of angiotensinogen.

Keywords: Angiotensin II (Ang II); Angiotensinogen; Kidney; Renin–angiotensin–aldosterone system (RAAS).

Fig. 1

Brief scheme of circulating renin–angiotensin–aldosterone system (RAAS) regulation. AGT angiotensinogen, Ang I angiotensin I, Ang II angiotensin II, JG cell juxtaglomerular cell, MR mineralocorticoid receptor

Fig. 2

Brief scheme of intrarenal renin–angiotensin–aldosterone system (RAAS) regulation. AGT angiotensinogen, Ang I angiotensin I, Ang II angiotensin II

Fig. 3

Effects of electrically stimulation of renal sympathetic nerve at 1 Hz (5 V, 1 msec) for 20 min on PRA, plasma des-Ang I-AGT/intact AGT ratio, and urinary des-Ang I-AGT/intact AGT ratio in anesthetized rats (n = 12–15). PRA plasma renin activity, AGT angiotensinogen, Ang I angiotensin I. *P < 0.05 vs. control