| Direct renin inhibition with aliskiren normalizes blood pressure in Cyp1a1-Ren2 transgenic rats with inducible angiotensin ii-dependent malignant hypertension. | |
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MedLine Citation:
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PMID: 21358304 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Cyp1a1-Ren2 transgenic rats [strain name: TGR(Cyp1a1Ren2)], administered indole-3-carbinol (I3C) develop angiotensin (ANG) II-dependent hypertension due to hepatic expression of the Ren2 renin gene. Although AT1 receptor blockade prevents the development of hypertension and normalizes the elevated arterial blood pressure of Cyp1-Ren2 rats, little information is available regarding the blood pressure and renal functional responses to direct inhibition of renin in this high circulating renin model of ANG II-dependent hypertension. This study was performed to determine the effects of acute direct renin inhibition with aliskiren on blood pressure and renal hemodynamics in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. METHODS: Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital-anesthetized male Cyp1a1-Ren2 rats during control conditions and after administration of the renin inhibitor, aliskiren (10 mg/kg, intravenous). RESULTS: Rats induced with I3C had higher MAP (194 ± 7 versus 141 ± 2 mm Hg, P < 0.001), lower renal plasma flow (RPF; 2.47 ± 0.23 versus 4.17 ± 0.35 mL/min/g, P < 0.001) and lower glomerular filtration rate (GFR; 1.01 ± 0.07 versus 1.34 ± 0.06 mL/min/g, P = 0.01) than noninduced Cyp1a1-Ren2 rats (n = 5). Aliskiren administration decreased MAP (194 ± 7 to 136 ± 2 mm Hg, P < 0.001) and increased RPF (2.47 ± 0.23 versus 4.31 ± 0.20 mL/min/g, P < 0.001) in hypertensive but not in normotensive rats, without altering GFR. CONCLUSIONS: Acute renin inhibition with aliskiren normalizes MAP and RPF in Cyp1a1-Ren2 rats with malignant hypertension. The normalization of MAP and RPF after acute renin inhibition indicates that renin generated by expression of the Ren2 gene is responsible for the maintenance of malignant hypertension and the associated reduction in renal hemodynamic function in Cyp1a1-Ren2 rats. |
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Authors:
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Catherine G Howard; 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; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of the medical sciences Volume: 341 ISSN: 1538-2990 ISO Abbreviation: Am. J. Med. Sci. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-26 Completed Date: 2011-06-23 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: 383-7 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, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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pharmacology* Angiotensin II / physiology* Animals Blood Pressure / drug effects*, physiology Cytochrome P-450 CYP1A1 / genetics*, physiology Disease Models, Animal Fumarates / pharmacology* Glomerular Filtration Rate / drug effects, physiology Hypertension, Malignant / physiopathology* Kidney / blood supply, drug effects, physiopathology Male Rats Rats, Transgenic Regional Blood Flow / drug effects, physiology Renin / antagonists & inhibitors*, genetics, physiology Vascular Resistance / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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2P20RR017659-06/RR/NCRR NIH HHS; HL26371/HL/NHLBI NIH HHS; R01 HL026371/HL/NHLBI NIH HHS; R01 HL026371-27/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Fumarates; 0/Ren2 protein, rat; 11128-99-7/Angiotensin II; 502FWN4Q32/aliskiren; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 3.4.23.15/Renin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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