Urinary angiotensinogen as an indicator of intrarenal angiotensin status in hypertension

被引:199
|
作者
Kobori, H [1 ]
Nishiyama, A [1 ]
Harrison-Bernard, LM [1 ]
Navar, LG [1 ]
机构
[1] Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA
关键词
angiotensin II; angiotensinogen; rats; kidney; urine; sodium; dietary; deoxycorticosterone acetate salt; Western blot;
D O I
10.1161/01.HYP.0000050102.90932.CF
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 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.
引用
收藏
页码:42 / 49
页数:8
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