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Endothelial Dysfunction in Chronic Myocardial Infarction Despite Increased Vascular Endothelial Nitric Oxide Synthase and Soluble Guanylate Cyclase Expression
- Source :
- Circulation. 100:292-298
- Publication Year :
- 1999
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1999.
-
Abstract
- Background —Endothelial dysfunction of the peripheral vasculature is a well-known phenomenon in congestive heart failure that contributes to the elevated peripheral resistance; however, the underlying mechanisms have not yet been clarified. Methods and Results —Dilator responses, the expression of protein and mRNA of the endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and soluble guanylate cyclase (sGC), and superoxide anion (O 2 − ) and peroxynitrite production were determined in aortic rings from Wistar rats 8 weeks after myocardial infarction and compared with those in sham-operated animals. In rats with heart failure, the concentration-response curve of the endothelium-dependent vasodilator acetylcholine (after preconstriction with phenylephrine) was significantly shifted to the right, and the maximum relaxation was attenuated. Determination of expression levels of the 2 key enzymes for NO-mediated dilations, eNOS and sGC, revealed a marked upregulation of both enzymes in aortas from rats with heart failure, whereas iNOS expression was not changed. Pretreatment with exogenous superoxide dismutase partially restored the acetylcholine-induced relaxation in aortas from rats with heart failure. Aortic basal and NADH-stimulated O 2 − production assessed by use of lucigenin-enhanced chemiluminescence was significantly elevated in rats with chronic myocardial infarction. Peroxynitrite-mediated nitration of protein tyrosine residues was not different between the 2 groups of rats. Conclusions —These results demonstrate that endothelial dysfunction in ischemic heart failure occurs despite an enhanced vascular eNOS and sGC expression and can be attributed to an increase in vascular O 2 − production by an NADH-dependent oxidase. By inactivation of NO, O 2 − production appears to be an essential mechanism for the endothelial dysfunction observed in heart failure.
- Subjects :
- medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
Vasodilator Agents
Myocardial Infarction
Aorta, Thoracic
Vasodilation
Phenylephrine
chemistry.chemical_compound
Superoxides
Enos
Physiology (medical)
Internal medicine
Renin
medicine
Animals
Rats, Wistar
Endothelial dysfunction
Heart Failure
Nitrates
biology
Superoxide Dismutase
business.industry
Superoxide
medicine.disease
biology.organism_classification
Acetylcholine
Rats
Up-Regulation
Nitric oxide synthase
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Guanylate Cyclase
biology.protein
Endothelium, Vascular
Nitric Oxide Synthase
Cardiology and Cardiovascular Medicine
business
Peroxynitrite
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....77050e5a605a0ddf566a275239fd088c