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Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome.
- Source :
-
Scientific reports [Sci Rep] 2020 Jan 21; Vol. 10 (1), pp. 889. Date of Electronic Publication: 2020 Jan 21. - Publication Year :
- 2020
-
Abstract
- Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26-28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3-4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative stress were comparable to wild-type. CD mice showed greater contractions to KCl. However, α1-adrenergic contractions to phenylephrine, but not with a thromboxane analogue, were compromised. Decreased phenylephrine responses were not affected by selective inducible NOS blockade with 1400 W, but were prevented by the non-selective NOS inhibitor L-NAME and the selective neuronal NOS inhibitor SMTC. Consistently, CD mice showed increased neuronal NOS expression in aortas. Overall, aortic stenosis in CD mice coexists with excessive nNOS-derived NO signaling that compromises ascending aorta α1-adrenergic contractions. We suggest that increased neuronal NOS signaling may act as a physiological 'brake' against the detrimental effects of stenosis.
- Subjects :
- Animals
Aorta, Thoracic drug effects
Aorta, Thoracic metabolism
Aortic Stenosis, Supravalvular physiopathology
Disease Models, Animal
Elastin metabolism
Endothelium, Vascular physiology
Ethidium analogs & derivatives
Ethidium blood
Male
Mice, Mutant Strains
Nitric Oxide metabolism
Nitric Oxide Synthase Type I metabolism
Oxidative Stress
Phenylephrine pharmacology
Receptors, Adrenergic, alpha-1 genetics
Williams Syndrome genetics
Williams Syndrome metabolism
Aorta, Thoracic physiopathology
Receptors, Adrenergic, alpha-1 metabolism
Williams Syndrome physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31965005
- Full Text :
- https://doi.org/10.1038/s41598-020-57803-3