Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in hypertension.
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.
Kobori
Hiroyuki
H
Department of Physiology, Tulane University Health Sciences Center, New Orleans, La 70112-2699, USA. hkobori@tulane.edu
Nishiyama
Akira
A
Harrison-Bernard
Lisa M
LM
Navar
L Gabriel
LG
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
D000906:Antibodies; D015415:Biomarkers; D000808:Angiotensinogen; D000804:Angiotensin II