| Enhanced urinary angiotensinogen excretion in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension. | |
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MedLine Citation:
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PMID: 20724906 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Carlo J Milani; Hiroyuki Kobori; John J Mullins; Kenneth D Mitchell |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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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:
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Created Date: 2010-11-04 Completed Date: 2010-12-10 Revised Date: 2013-01-16 |
Medline Journal Info:
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Nlm Unique ID: 0370506 Medline TA: Am J Med Sci Country: United States |
Other Details:
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Languages: eng Pagination: 389-94 Citation Subset: AIM; IM |
Affiliation:
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Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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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:
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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:
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0/Antihypertensive Agents; 0/Benzimidazoles; 0/Ren2 protein, rat; 0/Tetrazoles; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 139481-59-7/candesartan; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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