Document Detail


Cardiovascular hypertrophy in diabetic spontaneously hypertensive rats: optimizing blockade of the renin-angiotensin system.
MedLine Citation:
PMID:  12653675     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of the present study was to compare the antihypertrophic effects of blockade of the renin-angiotensin system (RAS), vasopeptidase inhibition and calcium channel antagonism on cardiac and vascular hypertrophy in diabetic spontaneously hypertensive rats (SHR). SHR with streptozotocin-induced diabetes were treated with one of the following therapies for 32 weeks: the angiotensin-converting enzyme (ACE) inhibitor captopril (100 mg/kg); the angiotensin AT(1) receptor antagonist valsartan (30 mg/kg); a combination of captopril with valsartan; the vasopeptidase inhibitor mixanpril (100 mg/kg); or the calcium channel antagonist amlodipine (6 mg/kg). Systolic blood pressure and cardiac and mesenteric artery hypertrophy were assessed. Mean systolic blood pressure in diabetic SHR (200+/-5 mmHg) was reduced by captopril (162+/-5 mmHg), valsartan (173+/-5 mmHg), mixanpril (176+/-2 mmHg) and amlodipine (159+/-4 mmHg), and was further reduced by the combination of captopril with valsartan (131+/-5 mmHg). Captopril, valsartan and mixanpril reduced heart and left ventricle weights by approx. 10%. The combination of captopril and valsartan further reduced heart weight (-24%) and left ventricular weight (-29%). Amlodipine did not affect cardiac hypertrophy. Only mixanpril and the combination of captopril and valsartan significantly reduced mesenteric weight. The mesenteric wall/lumen ratio was reduced by all drugs, and to a greater extent by the combination of captopril and valsartan. We conclude that optimizing the blockade of vasoconstrictive pathways such as the RAS, particularly with the combination of ACE inhibition and AT(1) receptor antagonism, is associated with antitrophic effects in the context of diabetes and hypertension. In contrast, calcium channel blockade, despite similar effects on blood pressure, confers less antitrophic effects in the diabetic heart and blood vessels.
Authors:
Markus Lassila; Belinda J Davis; Terri J Allen; Louise M Burrell; Mark E Cooper; Zemin Cao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  104     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-03-25     Completed Date:  2003-07-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  341-7     Citation Subset:  IM    
Affiliation:
Baker Heart Research Institute, P.O. Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
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MeSH Terms
Descriptor/Qualifier:
Alanine / analogs & derivatives*,  therapeutic use
Amiodarone / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Animals
Calcium Channel Blockers / therapeutic use
Captopril / therapeutic use
Cardiomegaly / blood,  etiology,  prevention & control*
Diabetes Mellitus, Experimental
Drug Therapy, Combination
Enzyme Inhibitors / therapeutic use
Hypertension / blood,  complications*,  drug therapy
Hypertrophy
Male
Mesenteric Arteries / pathology
Neprilysin / antagonists & inhibitors
Rats
Rats, Inbred SHR
Receptor, Angiotensin, Type 1
Receptors, Angiotensin / antagonists & inhibitors
Renin / blood
Renin-Angiotensin System / drug effects*
Tetrazoles / therapeutic use
Valine / analogs & derivatives*,  therapeutic use
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Calcium Channel Blockers; 0/Enzyme Inhibitors; 0/Receptor, Angiotensin, Type 1; 0/Receptors, Angiotensin; 0/Tetrazoles; 137862-53-4/valsartan; 156039-69-9/mixanpril; 1951-25-3/Amiodarone; 56-41-7/Alanine; 62571-86-2/Captopril; 7004-03-7/Valine; EC 3.4.23.15/Renin; EC 3.4.24.11/Neprilysin

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


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