Document Detail


Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats.
MedLine Citation:
PMID:  8564194     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Endothelin-1 gene expression is enhanced in aorta and mesenteric arteries, and possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt hypertensive rats but is normal or reduced in spontaneously hypertensive rats (SHR). Bosentan, a mixed ETA/ETB endothelin receptor antagonist, blunts the development of elevated blood pressure of DOCA-salt hypertensive rats but not in SHR. In this study we investigated whether treatment of DOCA-salt SHR with bosentan would result in blunted rise in blood pressure. 2. SHR, aged 13 weeks, were implanted with silastic containing DOCA and offered 1% saline to drink. Systolic blood pressure was measured by the tail-cuff method. Endothelin-1 mRNA abundance in aorta and mesenteric arteries was measured by Northern blot analysis. Content of immunoreactive endothelin in blood vessels was measured by radioimmunoassay. 3. Systolic blood pressure rose less in bosentan-treated DOCA-salt SHR (to 223 +/- 2 mmHg) in comparison to the untreated rats (241 +/- 1), a small but significant difference (P < 0.001). However, blood pressure of bosentan-treated DOCA-salt SHR was still higher than in age-matched SHR. Endothelin-1 mRNA abundance and content of immunoreactive endothelin were increased in the aorta and the mesenteric arterial bed of DOCA-salt SHR, and were unaffected by treatment with bosentan. 4. These data support the hypothesis of a role of endothelin-1 in blood pressure elevation in this hypertensive model with malignant hypertension. They also support the hypothesis that an antihypertensive effect of the mixed ETA/ETB endothelin receptor antagonist, bosentan, is found when experimental hypertensive animals exhibit enhanced endothelin-1 gene expression in blood vessels.
Authors:
E L Schiffrin; P Sventek; J S Li; A Turgeon; T Reudelhuber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  115     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1996-03-04     Completed Date:  1996-03-04     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1377-81     Citation Subset:  IM    
Affiliation:
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / drug effects,  metabolism
Base Sequence
Blood Pressure / drug effects
Blotting, Northern
Desoxycorticosterone
Endothelins / analysis*,  blood
Hypertension / blood,  chemically induced,  drug therapy*,  genetics
Mesenteric Arteries / drug effects,  metabolism
Molecular Sequence Data
RNA, Messenger / analysis*,  blood
Radioimmunoassay
Rats
Rats, Inbred SHR
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors*,  genetics
Sulfonamides / administration & dosage,  pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Endothelins; 0/RNA, Messenger; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Sulfonamides; 64-85-7/Desoxycorticosterone; Q326023R30/bosentan
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