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.

Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

“…A suppressed systemic renin-angiotensin system is commonly seen in subjects with salt-dependent hypertension [29]. Consistently, we have shown that HSD-fed DSS rats exhibit a marked decrease in plasma angiotensin II levels, accompanied by reduced plasma renin activity (PRA) [30,31]. Therefore, the reduced RAS activity may not contribute to the pathogenesis of the dipping pattern of BP in HSD-fed DSS rats.…”

Association of seminal angiotensinogen with sperm motility and morphology in male infertility

“…Renin–angiotensin system is known best for its role in the maintaining a balance of blood pressure, electrolyte and fluid homeostasis (Nishiyama & Kobori, ; Sparks et al, ). Nevertheless, the actions of the RAS reach beyond the scope of the cardiovascular system.…”

“…Renin–angiotensin system is mainly a blood‐borne hormone system, which regulates blood pressure, electrolyte and fluid homeostasis (Nishiyama & Kobori, ; Sparks, Crowley, Gurley, Mirotsou, & Coffman, ; Te Riet, Esch, Roks, Meiracker, & Danser, ). Intrinsic RAS exists in numerous tissues, which can adapt to specific local needs by adding to or differing from the circulating RAS.…”

Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

“…Inadequate RAS activation is crucial in the development of cardiovascular disease and chronic kidney disease (CKD) associated with diabetes [ 31 ]. In response to declining renal perfusion pressure and sodium delivery to distal tubules, juxtaglomerular cells markedly increase renin secretion [ 32 ]. SGLT2i can cause natriuresis in the early phase of treatment, which may activate systemic RAS.…”