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Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS
- Source :
- Basic Research in Cardiology, Basic Research in Cardiology, Springer Verlag, 2012, 107 (1), pp.1-9. ⟨10.1007/s00395-011-0240-6⟩
- Publication Year :
- 2011
-
Abstract
- International audience; Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.
- Subjects :
- neuronal nitric oxide synthase
Physiology
Duchenne muscular dystrophy
Vasodilation
MESH: Nitric Oxide Synthase Type I
Blood Pressure
Nitric Oxide Synthase Type I
030204 cardiovascular system & hematology
endothelial dysfunction
MESH: Dogs
chemistry.chemical_compound
Ventricular Dysfunction, Left
0302 clinical medicine
Enos
MESH: Ventricular Dysfunction, Left
MESH: Cyclic GMP
MESH: Animals
Endothelial dysfunction
Muscular dystrophy
Cyclic GMP
0303 health sciences
biology
MESH: Blood Pressure
medicine.anatomical_structure
Carotid Arteries
MESH: Endothelium, Vascular
Cardiology and Cardiovascular Medicine
MESH: Nitric Oxide Synthase Type III
medicine.medical_specialty
Endothelium
Nitric Oxide Synthase Type III
Bradykinin
Nitric Oxide
Article
03 medical and health sciences
Dogs
Physiology (medical)
Internal medicine
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
MESH: Muscular Dystrophy, Duchenne
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Cyclic guanosine monophosphate
030304 developmental biology
Duchenne muscular dystrophic cardiomyopathy
endothelial nitric oxide synthase
MESH: Bradykinin
MESH: Carotid Arteries
business.industry
medicine.disease
biology.organism_classification
Muscular Dystrophy, Duchenne
Disease Models, Animal
Endocrinology
chemistry
MESH: Nitric Oxide
Endothelium, Vascular
MESH: Disease Models, Animal
business
Subjects
Details
- ISSN :
- 14351803 and 03008428
- Volume :
- 107
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Basic research in cardiology
- Accession number :
- edsair.doi.dedup.....a9085ce6d78429f8a51dbe22c4e68d2b