Document Detail


Enhanced urinary angiotensinogen excretion in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension.
MedLine Citation:
PMID:  20724906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Previous studies have demonstrated that the urinary excretion of angiotensinogen is significantly increased in ANG II-infused hypertensive rats, which is associated with an augmentation of intrarenal ANG II levels. These findings suggest that urinary angiotensinogen excretion rates provide an index of intrarenal ANG II levels in ANG II-dependent hypertensive states. However, little information is available regarding the urinary excretion of angiotensinogen in ANG II-dependent malignant hypertension.
METHODS: This study was performed to determine if urinary angiotensinogen excretion is increased in Cyp1a1-Ren2 transgenic rats [strain name: TGR(Cyp1aRen2)] with inducible ANG II-dependent malignant hypertension. Adult male Cyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension.
RESULTS: Rats induced with I3C exhibited pronounced increases in systolic blood pressure (208 ± 7 versus 127 ± 3 mm Hg; P < 0.001), marked proteinuria (29.4 ± 3.6 versus 5.9 ± 0.3 mg/d; P < 0.001) and augmented urinary angiotensinogen excretion (996 ± 186 versus 241 ± 31 ng/d; P < 0.01). Chronic administration of the AT₁ receptor antagonist, candesartan (25 mg/L in drinking water, n = 6), prevented the I3C-induced increases in systolic blood pressure (125 ± 5 mm Hg; P < 0.001), proteinuria (7.3 ± 1.0 mg/d; P < 0.001) and urinary angiotensinogen excretion (488 ± 51 ng/d, P < 0.01).
CONCLUSIONS: These data demonstrate that the urinary excretion of angiotensinogen is markedly augmented in ANG II-dependent malignant hypertension. Such increased urinary angiotensinogen excretion may contribute to augmented intrarenal ANG II levels and, thereby, to the increased blood pressure in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension.
Authors:
Carlo J Milani; Hiroyuki Kobori; John J Mullins; Kenneth D Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The American journal of the medical sciences     Volume:  340     ISSN:  1538-2990     ISO Abbreviation:  Am. J. Med. Sci.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-10     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0370506     Medline TA:  Am J Med Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  389-94     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / metabolism*
Angiotensinogen / urine*
Animals
Antihypertensive Agents / therapeutic use
Benzimidazoles / therapeutic use
Blood Pressure / physiology
Body Weight
Cytochrome P-450 CYP1A1 / genetics*
Humans
Hypertension, Malignant / drug therapy,  urine*
Male
Middle Aged
Rats
Rats, Transgenic*
Renin / genetics*
Tetrazoles / therapeutic use
Grant Support
ID/Acronym/Agency:
2P20RR017659-06/RR/NCRR NIH HHS; DK072408/DK/NIDDK NIH HHS; HL26371/HL/NHLBI NIH HHS; R01 DK072408/DK/NIDDK NIH HHS; R01 DK072408-01A1/DK/NIDDK NIH HHS; R01 HL026371/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Benzimidazoles; 0/Ren2 protein, rat; 0/Tetrazoles; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 3.4.23.15/Renin; S8Q36MD2XX/candesartan
Comments/Corrections

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