Document Detail

Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension.
MedLine Citation:
PMID:  22261625     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: This study was performed to determine whether chronic direct renin inhibition can prevent the development of slowly progressive angiotensin (ANG) II-dependent hypertension and the associated derangements in renal function in Cyplal-Ren2 transgenic rats with inducible expression of the Ren2 gene.
METHODS: Male Cyplal-Ren2 rats (n = 6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamics and excretory function.
RESULTS: In rats induced with I3C, systolic blood pressure increased by day 3 (130 ± 7-160 ± 5 mm Hg, P < 0.01) and continued to increase to 191 ± 6 mm Hg (P < 0.001) by day 16. In a separate group of rats (n = 6), chronic administration of the direct renin inhibitor, aliskiren (30 mg/kg/d, sc), prevented the development of hypertension (113 ± 5 versus 114 ± 5 mm Hg, not significant). Rats treated with aliskiren exhibited significantly lower mean arterial pressure (138 ± 4 versus 201 ± 6 mm Hg, P < 0.001), renal vascular resistance (23 ± 4 versus 38 ± 3 mm Hg/mL/min · g, P < 0.01), urine flow (17.6 ± 1.4 versus 25.1 ± 2.9 μL/min, P < 0.05) and urinary sodium excretion (1.11 ± 0.32 versus 2.35 ± 0.28 μEq/min, P < 0.05) and higher renal plasma flow (4.22 ± 0.23 versus 2.56 ± 0.21 mL/min · g, P < 0.01) and glomerular filtration rate (1.19 ± 0.07 versus 0.78 ± 0.08 mL/min · g, P< 0.01), compared with induced rats not treated chronically with aliskiren.
CONCLUSIONS: The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated derangements in renal hemodynamics and excretory function in Cyplal-Ren2 transgenic rats.
Lily Huang; Catherine G Howard; 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:  344     ISSN:  1538-2990     ISO Abbreviation:  Am. J. Med. Sci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-21     Completed Date:  2013-04-15     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:  301-6     Citation Subset:  AIM; IM    
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MeSH Terms
Amides / pharmacology*,  therapeutic use
Angiotensin II / physiology
Arterial Pressure / drug effects*
Cytochrome P-450 CYP1A1 / metabolism
Fumarates / pharmacology*,  therapeutic use
Hypertension / genetics,  metabolism,  prevention & control*
Kidney / physiopathology*
Rats, Transgenic
Renin / antagonists & inhibitors*,  genetics,  metabolism
Grant Support
2P20RR017659-06/RR/NCRR NIH HHS; HL26371/HL/NHLBI NIH HHS; P20 RR017659/RR/NCRR NIH HHS; P20 RR017659-10/RR/NCRR NIH HHS; R01 HL026371/HL/NHLBI NIH HHS; R01 HL026371-23/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Amides; 0/Fumarates; 0/Ren2 protein, rat; 11128-99-7/Angiotensin II; 502FWN4Q32/aliskiren; EC P-450 CYP1A1; EC

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