Soluble Form of the (Pro) Renin Receptor Is Augmented in the Collecting Duct and Urine of Chronic Angiotensin II-Dependent Hypertensive Rats

Renin synthesis and secretion by principal cells of the collecting duct are enhanced in angiotensin (Ang) II-dependent hypertension. The presence of renin/(pro) renin and its receptor, the (pro) renin receptor ([P]RR), in the collecting duct may provide a pathway for Ang I generation with further conversion to Ang II. To assess whether (P) RR activation occurs during Ang II-dependent hypertension, we examined renal (P) RR levels and soluble (P) RR excretion in the urine of chronic Ang II-infused rats (80 ng/min; for 2 weeks; n=10) and sham-operated rats (n=10). Systolic blood pressure and Ang II levels in the plasma and kidney were increased whereas plasma renin activity was suppressed in Ang II-infused rats. Renal (P) RR transcripts were upregulated in the cortex and medulla of Ang II-infused rats. (P) RR immunoreactivity in collecting duct cells and the protein levels of the full-length form (37-kDa band) were significantly decreased in the medulla of Ang II-infused rats. The soluble (P) RR (28-kDa band) was detected in the renal medulla and urine samples of Ang II-infused rats, which also showed increases in urinary renin content. To determine whether the soluble (P) RR could stimulate Ang I formation, urine samples were incubated with recombinant human (pro) renin. Urine samples of Ang II-infused rats exhibited increased Ang I formation compared with sham-operated rats. Thus, in chronic Ang II-infused rats, the catalytic activity of the augmented renin produced in the collecting duct may be enhanced by the intraluminal soluble (P) RR and cell-surface located (P) RR, thus contributing to enhanced intratubular Ang II formation. (Hypertension. 2011;57:859-864.)