Document Detail


Nitric oxide pathway in hypertrophied heart: new therapeutic uses of nitric oxide donors.
MedLine Citation:
PMID:  20823718     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Left ventricular hypertrophy (LVH) is regarded as a complication common to a number of cardiovascular diseases, including hypertension, myocardial infarction and ischaemia associated with coronary artery disease. Initially LVH is a compensatory mechanism, but in the long term cardiac hypertrophy predisposes individuals to heart failure, myocardial infarction and sudden death. Alteration of the nitric oxide (NO) pathway is believed to play an important role in the haemodynamically overloaded heart and pathological cardiac remodelling. Although re-establishment of the physiological NO pathway could be considered an important therapeutic target, the use of conventional nitrates is limited in the clinical setting by the development of tissue resistance and tolerance and by the shortage of large-scale clinical trials unequivocally confirming the beneficial impact of NO donors on cardiovascular morbidity and mortality. The aim of this review is to present current therapeutic options for dealing with changes in the L-arginine-NO pathway. The most promising therapeutic approach is represented by a new neutral sugar organic nitrate, LA-419, the thiol group of which seems to protect NO from degradation, thereby increasing its bioavailability. In a model of aortic stenosis-induced pressure overload, LA-419 has been found to restore the complete NO signalling cascade and reduce left ventricular remodelling, but without restoring the original pressure gradient, indicating a possible direct antiproliferative effect. Future studies are needed to confirm this therapeutic benefit in other animal models of hypertension and in the clinical setting.
Authors:
Gema Ruiz-Hurtado; Carmen Delgado
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of hypertension     Volume:  28 Suppl 1     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2011-01-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  S56-61     Citation Subset:  IM    
Affiliation:
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Arginine / therapeutic use
Biopterin / analogs & derivatives,  therapeutic use
Cardiomegaly / drug therapy,  enzymology,  metabolism*
Cyclic GMP / metabolism
Humans
Nitric Oxide / metabolism*
Nitric Oxide Donors / therapeutic use*
Nitric Oxide Synthase / metabolism
Chemical
Reg. No./Substance:
0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 74-79-3/Arginine; 7665-99-8/Cyclic GMP; EC 1.14.13.39/Nitric Oxide Synthase

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