Role of Collecting Duct Renin in the Pathogenesis of Hypertension.
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 (Ca2+) 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.
['Gonzalez|Alexis A|AA|', 'Lara|Lucienne S|LS|', 'Prieto|Minolfa C|MC|']
D000804:Angiotensin II D000818:Animals D006801:Humans D006973:Hypertension D007685:Kidney Tubules, Collecting D007686:Kidney Tubules, Distal D007687:Kidney Tubules, Proximal D012083:Renin D012084:Renin-Angiotensin System
Hypertension Prorenin Prorenin receptor Intracellular signaling Kidney