Document Detail


Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension.
MedLine Citation:
PMID:  23232645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the antihypertensive effects of valsartan, aliskiren, or both drugs combined on circulating, cardiac, and renal components of the renin-angiotensin system in congenic mRen2.Lewis hypertensive rats assigned to: vehicle (n=9), valsartan (via drinking water, 30 mg/kg per day; n=10), aliskiren (SC by osmotic mini-pumps, 50 mg/kg per day; n=10), or valsartan (30 mg/kg per day) combined with aliskiren (50 mg/kg per day; n=10). Arterial pressure and heart rate were measured by telemetry before and during 2 weeks of treatment; trunk blood, heart, urine, and kidneys were collected for measures of renin-angiotensin system components. Arterial pressure and left-ventricular weight/tibia length ratio were reduced by monotherapy of valsartan, aliskiren, and further reduced by the combination therapy. Urinary protein excretion was reduced by valsartan and further reduced by the combination. The increases in plasma angiotensin (Ang) II induced by valsartan were reversed by the treatment of aliskiren and partially suppressed by the combination. The decreases in plasma Ang-(1-7) induced by aliskiren recovered in the combination group. Kidney Ang-(1-12) was increased by the combination therapy whereas the increases in urinary creatinine mediated by valsartan were reversed by addition of aliskiren. The antihypertensive and antiproteinuric actions of the combined therapy were associated with marked worsening of renal parenchymal disease and increased peritubular fibrosis. The data show that despite improvements in the surrogate end points of blood pressure, ventricular mass, and proteinuria, dual blockade of Ang II receptors and renin activity is accompanied by worsening of renal parenchymal disease reflecting a renal homeostatic stress response attributable to loss of tubuloglomerular feedback by Ang II.
Authors:
Norihito Moniwa; Jasmina Varagic; Sarfaraz Ahmad; Jessica L VonCannon; Stephen W Simington; Hao Wang; Leanne Groban; K Bridget Brosnihan; Sayaka Nagata; Johji Kato; Kazuo Kitamura; R Ariel Gomez; Maria L Sequeira Lopez; Carlos M Ferrario
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-10
Journal Detail:
Title:  Hypertension     Volume:  61     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-03-20     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  417-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology*,  therapeutic use
Angiotensin II / blood
Angiotensin II Type 1 Receptor Blockers / pharmacology*,  therapeutic use
Animals
Antihypertensive Agents / pharmacology*,  therapeutic use
Blood Pressure / drug effects,  physiology
Drug Therapy, Combination
Fumarates / pharmacology*,  therapeutic use
Heart Rate / drug effects,  physiology
Hemodynamics / drug effects,  physiology
Hypertension / blood,  drug therapy*,  physiopathology
Kidney / drug effects,  metabolism
Male
Rats
Renin / antagonists & inhibitors*
Renin-Angiotensin System / drug effects*,  physiology
Telemetry
Tetrazoles / pharmacology*,  therapeutic use
Valine / analogs & derivatives*,  pharmacology,  therapeutic use
Grant Support
ID/Acronym/Agency:
AG-033727/AG/NIA NIH HHS; HL-051952/HL/NHLBI NIH HHS; P01 HL051952/HL/NHLBI NIH HHS; R01 AG033727/AG/NIA NIH HHS; R01 DK091330/DK/NIDDK NIH HHS; R37 HL066242/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Amides; 0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Fumarates; 0/Tetrazoles; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 502FWN4Q32/aliskiren; EC 3.4.23.15/Renin; HG18B9YRS7/Valine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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