Document Detail


Vasorelaxant effects of a nitric oxide-releasing aspirin derivative in normotensive and hypertensive rats.
MedLine Citation:
PMID:  11498517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension and to interfere with the effectiveness of some anti-hypertensive therapies. In this study, we tested the effects of a gastric-sparing, nitric oxide-releasing derivative of aspirin (NCX-4016) on hypertension in rats. 2. Hypertension was induced by administering L-NAME in the drinking water (400 mg l(-1)). Groups of rats were treated daily with aspirin, NCX-4016 or vehicle. 3. NCX-4016 significantly reduced blood pressure relative to the aspirin-treated group over the 2-week period of treatment. Aspirin and, to a lesser extent, NCX-4016 suppressed whole blood thromboxane synthesis. 4. In anaesthetized rats, acute intravenous administration of NCX-4016 caused a significant fall in mean arterial pressure in hypertensive rats, but was devoid of such effects in normotensive controls. 5. In vitro, NCX-4016 relaxed phenylephrine-pre-contracted aortic rings obtained from both normotensive and hypertensive rats, and significantly reduced their responsiveness to the contractile effects of phenylephrine. 6. These results suggest that NCX-4016 reduces blood pressure in hypertensive rats, not simply through the direct vasodilatory actions of the nitric oxide released by this compound, but also through possible interference with the effects of endogenous pressor agents. These properties, added to its anti-thrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients.
Authors:
M N Muscará; F Lovren; W McKnight; M Dicay; P del Soldato ; C R Triggle; J L Wallace
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  133     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-10     Completed Date:  2001-10-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1314-22     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo, 05508-900, SP, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics,  pharmacology*
Aorta / drug effects,  metabolism,  physiology,  physiopathology
Aspirin / analogs & derivatives,  pharmacokinetics,  pharmacology*
Blood Pressure / drug effects*
Consciousness
Dose-Response Relationship, Drug
Hypertension / physiopathology*
Male
NG-Nitroarginine Methyl Ester / pharmacology
Nitrates / metabolism
Nitric Oxide / metabolism*
Nitrites / metabolism
Nitroprusside / pharmacology
Phenylephrine / pharmacology
Rats
Rats, Wistar
Renin / blood
Thromboxanes / metabolism
Vasodilation / drug effects*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Nitrates; 0/Nitrites; 0/Thromboxanes; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 175033-36-0/nitroaspirin; 50-78-2/Aspirin; 50903-99-6/NG-Nitroarginine Methyl Ester; 59-42-7/Phenylephrine; EC 3.4.23.15/Renin
Comments/Corrections

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