Document Detail

Cardiovascular changes in spontaneously hypertensive rats are improved by chronic treatment with zofenopril.
MedLine Citation:
PMID:  19917062     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR).
EXPERIMENTAL APPROACH: Male SHR were treated with 0.5 or 10 mg kg(-1) per day of zofenopril (Z(0.5) and Z(10)) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta.
RESULTS: Long-term daily administration of zofenopril (10 mg kg(-1)) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg kg(-1) per day of zofenopril slightly modified blood pressure and the other effects were weaker.
CONCLUSIONS AND IMPLICATIONS: Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects.
M Gómez-Roso; M J Montero; R Carrón; M A Sevilla
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  158     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-03-12     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1911-21     Citation Subset:  IM    
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / administration & dosage,  pharmacology
Antihypertensive Agents / administration & dosage,  pharmacology*
Antioxidants / administration & dosage,  pharmacology
Blood Pressure / drug effects*
Captopril / administration & dosage,  analogs & derivatives*,  pharmacology
Cardiomegaly / etiology,  prevention & control
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects,  metabolism
Hypertension / complications,  drug therapy*
Rats, Inbred SHR
Rats, Inbred WKY
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Antioxidants; 62571-86-2/Captopril; 81872-10-8/zofenopril

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