title: Soluble form of the (pro)renin receptor is augmented in the collecting duct and urine of chronic angiotensin II-dependent hypertensive rats.
abstract: 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.
authors.affiliation: Department of Physiology, Tulane University, School of Medicine, 1430 Tulane Ave, SL39, New Orleans, LA 70112, USA.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Lucienne S
authors.initials: LS
authors.lastname: Lara
authors.forename: Christina
authors.initials: C
authors.lastname: Luffman
authors.forename: Dale M
authors.initials: DM
authors.lastname: Seth
authors.forename: Minolfa C
authors.initials: MC
authors.lastname: Prieto
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin; D000093342:Prorenin Receptor