Document Detail


Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan).
MedLine Citation:
PMID:  7955209     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Endothelin (ET) is a potent vasoconstrictor, and its concentration is increased in patients with heart failure. The purpose of this study was to investigate the role of endothelin in heart failure by use of a rat model.
METHODS AND RESULTS: Experiments were performed on rats at 1 through 16 weeks after sham operation or coronary artery ligation. Rats with left ventricular end-diastolic pressures > 15 mm Hg were considered to have chronic heart failure (CHF), while the others were considered to have uncomplicated myocardial infarction (MI). There were increased ET-1 concentrations in CHF rats at weeks 1 to 16 (Sham, 20 +/- 0.5 pg/mL, n = 45; CHF, 31 +/- 2 pg/mL, n = 50; P < .001) and transient increases in ET-3 concentrations at week 1 in both the MI and CHF groups. There were no significant increases in big ET-1 concentrations, suggesting an increased conversion of ET-1 from big ET-1 in the CHF group. At weeks 2 through 8, oral administration of the mixed (ETA and ETB) endothelin receptor antagonist bosentan significantly decreased mean arterial pressure in conscious CHF rats, an effect that increased over time. Furthermore, bosentan had an additive effect to the angiotensin-converting enzyme inhibitor cilazapril.
CONCLUSIONS: Endothelin plays a role in the maintenance of blood pressure in CHF rats, as evidenced by the significant reduction in mean arterial pressure after oral administration of bosentan. Therefore, endothelin antagonists may be useful therapeutic agents in the treatment of CHF.
Authors:
J R Teerlink; B M Löffler; P Hess; J P Maire; M Clozel; J P Clozel
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation     Volume:  90     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-12-16     Completed Date:  1994-12-16     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2510-8     Citation Subset:  AIM; IM    
Affiliation:
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects*
Chronic Disease
Cilazapril / pharmacology
Endothelins / blood,  physiology*
Heart Failure / physiopathology*
Male
Rats
Rats, Wistar
Receptors, Endothelin / antagonists & inhibitors*
Sulfonamides / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Endothelins; 0/Receptors, Endothelin; 0/Sulfonamides; 92077-78-6/Cilazapril; Q326023R30/bosentan

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


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