title: Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in hypertension.
abstract: Angiotensin II (AngII) infusions augment renal angiotensinogen mRNA and protein and urinary angiotensinogen excretion (U(AGT)). Further experiments were performed in 4 groups of rats: normal salt diet with sham operation, NS+Sham, n=6; NS with AngII infusion at 40 ng/min via osmotic minipump, NS+AngII(40), n=9; NS with AngII infusion at 80 ng/min, NS+AngII(80), n=9; high-salt diet with deoxycorticosterone acetate salt pellet (100 mg), HS+DOCA, n=4. These experiments sought to determine whether enhanced U(AGT) is specifically associated with increased kidney AngII levels or is a nonspecific consequence of the hypertension. Systolic BP (SBP) was significantly increased to 131+/-2 and 162+/-2 mm Hg at day 11 in NS+AngII(40) and NS+AngII(80), respectively, compared with NS+Sham (110+/-1). Regression analysis demonstrated a positive relationship (R=0.49) between SBP and U(AGT) for NS+Sham (1.1+/-0.3 nmol AngI/d), NS+AngII(40) (2.5+/-0.9), and NS+AngII(80) (5.5+/-1.5). U(AGT) was also highly correlated (R=0.70) with kidney AngII content for NS+Sham (49+/-6 fmol/g), NS+AngII(40) (215+/-49), and NS+AngII(80) (347+/-47); but not with plasma AngII (R=0.12). HS+DOCA rats also exhibited increased SBP to 134+/-1 mm Hg, but U(AGT) (1.4+/-0.4 nmol AngI/d) and intrarenal AngII content (13+/-2 fmol/g) were not increased despite the hypertension. Infused human angiotensinogen could not be detected in urine of sham-operated or AngII-infused rats (n=4 each). These data demonstrate that U(AGT) increases in AngII-dependent hypertension in a dose- and time-dependent manner, but not in hypertension elicited by HS+DOCA. The results support the hypothesis that AngII-dependent hypertension results in elevated intrarenal AngII and angiotensinogen levels, reflected by increased U(AGT), which does not occur in an AngII-independent hypertensive model.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, New Orleans, La 70112-2699, USA. hkobori@tulane.edu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Harrison-Bernard
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000032:analysis* / Q000494:pharmacology; D000808:Angiotensinogen / Q000276:immunology / Q000494:pharmacology / Q000652:urine*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000652:urine*; D007668:Kidney / Q000737:chemistry*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000906:Antibodies; D015415:Biomarkers; D000808:Angiotensinogen; D000804:Angiotensin II