Abstract P264: Interaction of Collecting Duct-Derived Prorenin and Soluble Prorenin Receptor Increases Intraluminal Renin Activity and Augments Intratubular Angiotensin II Formation in Ang II-Dependent Hypertensive Rats
Upregulation of collecting duct (CD)-derived renin (CD renin) in angiotensin II (Ang II)-dependent hypertension may provide a pathway for intratubular Ang II formation by acting on angiotensinogen (AGT) delivered from proximal tubule segments. Recently, a prorenin/renin receptor (PRR) has been cloned and shown to enhance renin and prorenin activation. The soluble form of the PRR (sPRR) is augmented in the renal inner medulla of chronic Ang II-infused rats. The present study was performed to determine if renin is secreted into the lumen by the CD cells in chronic Ang II-infused rats and to establish the functional contribution of sPRR to the enhanced renin activity in distal nephron segments. Accordingly, urinary levels of renin (uRen) and Ang II (uAngII) were measured by RIA in chronic Ang II-infused male Sprague-Dawley rats [80 ng/min, SC minipumps for 14 d, n=10] and sham-operated rats [n=10]. Systolic blood pressure increased in the Ang II rats by Day 5 and continued to increase throughout the study (Day 13; Ang II: 175±10 vs. sham: 116±2 mmHg; p<0.05). Although plasma renin activity (PRA) was suppressed in the Ang II-infused rats, renal medullary renin content was significantly augmented (12,605±1,343 vs. 7,956±765 ng Ang I/h/mg;p<0.05). The excretion of uAngII was also increased (3,813±431 vs. 2,080±361 fmol/day; p<0.05). In addition, renin and prorenin excretion rates increased progressively and were markedly augmented by Day 13 of Ang II infusion [renin (8.6±1.5 vs. 2.8±0.5x10-6Enzyme Units Excreted (EUE) /day; prorenin: 15.8 ± 2.8 vs. 2.6 ± 0.7x10-3 EUE /day, p<0.05). Renin and prorenin protein levels examined by Western Blot in the urine were similarly increased. Importantly, the incubation of urine samples of Ang II-infused rats with recombinant human prorenin showed increased Ang I formation compared to sham-operated rats. In conclusion, in chronic Ang II-infused rats, the presence of sPRR in the urine reflects augmented enzymatic activity of prorenin secreted by the principal cells of the CD, which increase intratubular Ang II de novo formation in the distal nephron segments thus contributing to enhanced sodium reabsorption during Ang II-dependent hypertension.
- © 2011 by American Heart Association, Inc.