on November 25, 2002
Published online before print November 25, 2002, doi: 10.1161/01.HYP.0000050102.90932.CF
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Submitted on August 12, 2002
From the Department of Physiology, Tulane University Health Sciences Center, New Orleans, La. * To whom correspondence should be addressed. E-mail: hkobori{at}tulane.edu.
Abstract—Angiotensin II (AngII) infusions augment renal angiotensinogen mRNA and protein and urinary angiotensinogen excretion (UAGT). 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 UAGT 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 UAGT 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). UAGT 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 UAGT (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 UAGT 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 UAGT, which does not occur in an AngII-independent hypertensive model.
Revised on September 13, 2002
Urinary Angiotensinogen as an Indicator of Intrarenal Angiotensin Status in Hypertension
Hiroyuki Kobori*;
Key words: angiotensin II • angiotensinogen • rats • kidney • urine • sodium, dietary • deoxycorticosterone acetate salt • Western blot
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