Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice

Autor: Sumathy Mohan, Preethi Janardhanan, Kaiwalya S Deo, Saurav B. Chandra, Timothy Q. Duong, Bridget M. Ford, Eric R. Muir, Linlin Cong, Lei Huang
Rok vydání: 2015
Předmět:
0301 basic medicine
Genetically modified mouse
endocrine system
medicine.medical_specialty
endocrine system diseases
Nitric Oxide Synthase Type III
Gene Expression
Blood Pressure
Mice
Transgenic
Nitric oxide
Diabetes Mellitus
Experimental
03 medical and health sciences
chemistry.chemical_compound
Basal (phylogenetics)
Mice
Enos
Internal medicine
Diabetes mellitus
medicine
Animals
Molecular Targeted Therapy
Endothelial dysfunction
biology
business.industry
Body Weight
Endothelial Cells
Original Articles
medicine.disease
biology.organism_classification
Cerebrovascular Disorders
030104 developmental biology
Endocrinology
Blood pressure
Diabetes Mellitus
Type 1
Neurology
chemistry
Cerebral blood flow
Anesthesia
Cerebrovascular Circulation
Neurology (clinical)
Endothelium
Vascular
Cardiology and Cardiovascular Medicine
business
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 36(6)
ISSN: 1559-7016
Popis: Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2Akita+/−), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2Akita+/−) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2Akita+/− and TgeNOS-Ins2Akita+/− were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2Akita+/− mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2Akita+/− was significantly higher compared with the Ins2Akita+/− and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target.
Databáze: OpenAIRE
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