Intratubular Renin-Angiotensin System in Hypertension

Abstract

It is well recognized that the renin-angiotensin system plays an important role in the regulation of arterial pressure and sodium homeostasis. Recent years, many studies have shown that local tissue angiotensin II levels are differentially regulated and cannot be explained on the basis of circulating concentrations. All of the components needed for angiotensin II generation are present within the various compartments in the kidney including the renal interstitium and the tubular network. The cascade of the renin-angiotensin system demonstrates three major possible sites for the pharmacological interruption of the renin-angiotensin system: the interaction of renin with its substrate, angiotensinogen, the angiotensin converting enzyme, and angiotensin II type 1 receptors. This brief article will focus on the role of the intratubular renin-angiotensin system in the pathophysiology of hypertension and the responses to the renin-angiotensin system blockade by renin inhibitors, angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers.

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…The RAS has been acknowledged as an endocrine, paracrine, autocrine, and intracrine system Re, 2003;Kobori et al, 2006;Re and Cook, 2006;Suzaki et al, 2006b), and, thus, it has been difficult to delineate the quantitative contributions of systemically delivered versus locally formed Ang peptides to the levels existing in any given tissue. Emerging evidence suggests that local formation is of major significance in the regulation of the Ang levels in many organs and tissues.…”

Succinate Receptors in the Kidney

“…As such, SUCNR1 may allow the body to escape from the angiotensin II-negative feedback loop and maintain high levels of (pro)renin, thereby contributing to sustained hypertension. [25][26][27] Nowadays, it is well established that the production and release of renin is no longer restricted to the JGA, and individual components of the renin-angiotensin system have been detected throughout the nephron. 28 The function of this paracrine tubular renin-angiotensin system is slowly emerging.…”

“…28 The function of this paracrine tubular renin-angiotensin system is slowly emerging. 24,26 In the kidney of diabetic mice, activation of SUCNR1 in the cTAL 20 and CD 19 leads to increased ERK1/2 phosphorylation, whereas this effect is absent in SUCNR1 Ϫ/Ϫ mice.…”

Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An Update

“…Apart from the well known systemic RAS, production of multiple RAS components has been found in a variety of tissues including the kidney. 2,3 Inappropriate activation of intrarenal RAS has been recognized as an important mechanism for hypertension and renal disease. To date, the anti-RAS regimen represents the cornerstone therapy for both diseases.…”