Document Detail


Direct renin inhibition with aliskiren normalizes blood pressure in Cyp1a1-Ren2 transgenic rats with inducible angiotensin ii-dependent malignant hypertension.
MedLine Citation:
PMID:  21358304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Catherine G Howard; John J Mullins; Kenneth D Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2011-04-26     Completed Date:  2011-06-23     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0370506     Medline TA:  Am J Med Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  383-7     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Amides / 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:
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:
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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