Document Detail

Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.
MedLine Citation:
PMID:  11904522     Owner:  NLM     Status:  MEDLINE    
Enrasentan is an antagonist of endothelin (ET) receptors. Previous studies have shown that antagonism of ET receptors might represent a new approach to the treatment of hypertension. Rats with a high-fructose diet (HFD) develop hyperinsulinemia, hypertriglyceridemia, and hypertension; renal and cardiac damage. The aim of this study was to evaluate whether enrasentan could reverse the hypertension and reduce the target organ damage induced by an HFD. Fifty-five WKY rats were divided into 6 groups; 35 animals received HFD for a month; thereafter 5 animals were killed, and the others were treated either with enrasentan (n = 10), hydralazine (n = 10), or placebo (n = 10) for a further month while on the HFD. Twenty animals were kept on a standard diet throughout the study; either placebo (n = 10) or enrasentan (n = 10) was administered during the second month. Enrasentan and hydralazine completely eliminated the HFD-induced increase in blood pressure; however, only enrasentan reduced the renal and cardiac damage caused by the diet. In conclusion, enrasentan was effective both in normalizing blood pressure and in reducing renal and cardiac damage; the organ protection cannot be attributed solely to the antihypertensive effect, because it was absent in the case of hydralazine, despite successful control of blood pressure.
Alessandro Cosenzi; E Bernobich; M Bonavita; G Bertola; R Trevisan; G Bellini
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  39     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-20     Completed Date:  2002-07-29     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  488-95     Citation Subset:  IM    
Dipartimento di Medicina Clinica e Neurologia, Ospedale di Cattinara, Università di Trieste, Strada di Fiume, 31400 Trieste, Italy.
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MeSH Terms
Blood Pressure / drug effects*
Body Weight / drug effects
Carboxylic Acids / therapeutic use*
Collagen / metabolism
Dietary Carbohydrates / administration & dosage
Disease Models, Animal
Fructose / administration & dosage
Hyperinsulinism / chemically induced,  complications,  drug therapy*,  physiopathology
Hypertension / chemically induced,  complications,  drug therapy*,  physiopathology
Indans / therapeutic use*
Kidney / drug effects,  metabolism,  pathology
Myocardium / metabolism,  pathology
Rats, Inbred WKY
Receptors, Endothelin / antagonists & inhibitors
Reg. No./Substance:
0/Carboxylic Acids; 0/Dietary Carbohydrates; 0/Indans; 0/Receptors, Endothelin; 0/SB 217242; 30237-26-4/Fructose; 9007-34-5/Collagen

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