Role of Collecting Duct Renin in the Pathogenesis of Hypertension

Abstract

The presence of renin production by the principal cells of the collecting duct has opened new perspectives for the regulation of intrarenal angiotensin II (Ang II). Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are present in the tubular fluid coming from the proximal tubule and collecting duct. All the components needed for Ang II formation are present along the nephron, and much is known about the mechanisms regulating renin in juxtaglomerular cells (JG); however, those in the collecting duct remain unclear. Ang II suppresses renin via protein kinase C (PKC) and calcium (Ca) in JG cells, but in the principal cells, Ang II increases renin synthesis and release through a pathophysiological mechanism that increases further intratubular Ang II de novo formation to enhance distal Na reabsorption. Transgenic mice overexpressing renin in the collecting duct demonstrate the role of collecting duct renin in the development of hypertension. The story became even more interesting after the discovery of a specific receptor for renin and prorenin: the prorenin receptor ((P)RR), which enhances renin activity and fully activates prorenin. The interactions between (P)RR and prorenin/renin may further increase intratubular Ang II levels. In addition to Ang II, other mechanisms have been described in the regulation of renin in the collecting duct, including vasopressin (AVP), bradykinin (BK), and prostaglandins. Current active investigations are aimed at elucidating the mechanisms regulating renin in the distal nephron segments and understand its role in the pathogenesis of hypertension.

Effects of maternal fructose intake on the offspring’s kidneys

“…In addition to its synthesis and release by juxtaglomerular cells, renin is also produced by the principal cells of the connecting tubules and collecting ducts in rat, mouse, and human kidneys ( Hackenthal et al, 1990 ; Rohrwasser et al, 1999 ; Prieto-Carrasquero et al, 2004 ). In experimental models with high levels of angiotensin II (ANG II), juxtaglomerular renin is suppressed, although its expression increases in the distal nephron ( Gonzalez et al, 2017 ). Renin produced in the late nephron segments may act on angiotensinogen delivered from proximal segments, generating angiotensin I, which, under the action of ACE1 existing in the collecting duct, may contribute to the increase in the generation of ANG II ( Casarini et al, 1997 ; Casarini et al, 2001 ).…”

Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control

“…In summary, the available evidence supports the concept of the circulating (endocrine), local tissue (paracrine), and intracellular RAS system in the kidney. All major components of the RAS, including AGT [5,38–40,55,71,72], renin and prorenin [17,18,25,35,41,49–54,157], ACE [7,8,42,90–96,98,99,104,111,112] and ACE2 [19,20,34,48,], ANG II and other ANG metabolites [37,46,47,55–61], AT 1 , AT 2 and the ANG (1–7)/Mas receptors [79,92,93,123,124,131–136,156], have been identified, especially in the proximal tubule. Their respective sources and roles in the cardiovascular and kidney, and blood pressure regulation have been extensively investigated using molecular, cellular, genetic and pharmacological approaches during last three decades.…”

Targeted neurotransmitter metabolomics profiling of oleanolic acid in the treatment of spontaneously hypertensive rats

“…It is associated with a variety of pathological disorders including neurotransmitter changes, disordered angiotensin levels, impaired endothelial functions, and overexcited sympathetic nerves as well as other processes such as inammatory factors and oxidative stress. [31][32][33] OA has a signicant antihypertensive effect on hypertensive animals, and its antihypertensive mechanism mainly involves the inhibition of vascular smooth muscle cell proliferation and inammation of the blood vessel wall, thus reducing blood vessel stenosis caused by balloon catheter injury and other causes. [34][35][36] Despite extensive studies, its mechanism associated with neuropathology remains completely unclear.…”