Document Detail


Hydralazine decreases sodium nitroprusside-induced rat aortic ring relaxation and increased cGMP production by rat aortic myocytes.
MedLine Citation:
PMID:  15985267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Association of hydralazine with nitrova-sodilators has long been known to be beneficial in the vasodilator treatment of heart failure. We previously found that hydralazine appeared to reduce the increase in cGMP induced by sodium nitroprusside in cultured rat aortic myocytes. In order to further explore this seemingly paradoxical interaction, we extended our initial observations in rat aortic myocytes and also determined the influence of hydralazine on sodium nitroprusside-induced relaxation of rat aortic rings. Hydralazine produced a concentration-dependent inhibition of sodium nitroprusside stimulation of cGMP production and caused a rightward shift of concentration-relaxation curves in aortic rings. A possible mechanism of the hydralazine-nitroprusside interaction could be the interference with bioactivation of the nitro-vasodilator to release nitric oxide. Recent evidence indicates that vascular NADH oxidase, an enzyme known to be inhibited by hydralazine, could be involved in this process. Accordingly, hydralazine was found to inhibit NADH oxidase activity in rat aortic myocytes at concentrations similar to those reducing sodium nitroprusside responses. It was concluded that antagonism of sodium nitroprusside action by hydralazine could be a consequence of interference with bioactivation of the former, apparently through inhibition of vascular NADH oxidase.
Authors:
Horacio Vidrio; Pilar González-Romo; Ezequiel Alvarez; Carlos Alcaide; Francisco Orallo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-06-27
Journal Detail:
Title:  Life sciences     Volume:  77     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-11-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  3105-16     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Apartado Postal 70297, 04510 Mexico, D.F., México. vidrio@servidor.unam.mx
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / cytology,  drug effects*,  metabolism
Cells, Cultured
Cyclic GMP / metabolism*
Endothelium, Vascular / cytology,  drug effects,  metabolism
Hydralazine / chemistry,  pharmacology*
Male
Multienzyme Complexes / antagonists & inhibitors,  metabolism
Muscle Relaxation / drug effects,  physiology
Myocytes, Cardiac / cytology,  drug effects*,  metabolism
NADH, NADPH Oxidoreductases / antagonists & inhibitors,  metabolism
Nitric Oxide / metabolism
Nitroprusside / chemistry,  pharmacology*
Rats
Rats, Wistar
Vasodilation / drug effects
Vasodilator Agents / chemistry,  pharmacology*
Chemical
Reg. No./Substance:
0/Multienzyme Complexes; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 7665-99-8/Cyclic GMP; 86-54-4/Hydralazine; EC 1.6.-/NADH oxidase; EC 1.6.-/NADH, NADPH Oxidoreductases

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


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