Document Detail

Raloxifene enhances nitric oxide release in rat aorta via increasing endothelial nitric oxide mRNA expression.
MedLine Citation:
PMID:  11779577     Owner:  NLM     Status:  MEDLINE    
We report the modulatory effects of chronic oral LY139481 (raloxifene) on basal release of nitric oxide (NO) and mRNA levels of endothelial NO synthase (eNOS) in rat thoracic aorta. Constrictor dose-response curves to phenylephrine were generated before and after pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Aortic segments were obtained from four groups of rats gavaged orally for 21 days: (i) ovariectomized, (ii) sham, (iii) ovariectomized estradiol-treated, and (iv) ovariectomized raloxifene-treated. Intact aortic rings from sham rats and ovariectomized rats receiving raloxifene and estrogen showed a greater potentiation of the phenylephrine responses after L-NAME. Semi-quantitative reverse transcription-polymerase chain reaction indicated a gender-based difference in eNOS mRNA expression in thoracic aorta. Moreover, we demonstrated that eNOS mRNA expression in the upper thoracic aorta was significantly higher in treatment groups. These results show that chronically administered raloxifene is exerting a potentially important vasculo-protective effect by stimulating eNOS expression.
Roshanak Rahimian; Gregory P Dubé; Warda Toma; Nancy Dos Santos; Bruce M McManus; Cornelis van Breemen
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  434     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-07     Completed Date:  2002-04-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  141-9     Citation Subset:  IM    
The Vancouver Vascular Biology Research Center, University of British Columbia, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada.
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MeSH Terms
Acetylcholine / pharmacology
Aorta, Thoracic / drug effects*,  enzymology,  metabolism
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects*,  metabolism*,  physiology,  physiopathology
Estrogen Receptor Modulators / pharmacology*
Estrogens / pharmacology
Muscle Contraction / drug effects
Nitric Oxide / biosynthesis*,  genetics
Nitric Oxide Synthase / biosynthesis,  genetics
Nitric Oxide Synthase Type III
Phenylephrine / pharmacology
RNA, Messenger / biosynthesis*
Raloxifene / pharmacology*
Rats, Sprague-Dawley
Vasodilation / drug effects,  physiology
Reg. No./Substance:
0/Estrogen Receptor Modulators; 0/Estrogens; 0/RNA, Messenger; 10102-43-9/Nitric Oxide; 51-84-3/Acetylcholine; 59-42-7/Phenylephrine; 84449-90-1/Raloxifene; EC Oxide Synthase; EC Oxide Synthase Type III; EC protein, rat

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

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