title: Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice.
abstract: 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 (Ins2(Akita+/-)), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2(Akita+/-)) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2(Akita+/-) and TgeNOS-Ins2(Akita+/-) 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 Ins2(Akita+/-) mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2(Akita+/-) was significantly higher compared with the Ins2(Akita+/-) 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.
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Saurav B
authors.initials: SB
authors.lastname: Chandra
authors.affiliation: Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Sumathy
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Ford
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Preethi
authors.initials: P
authors.lastname: Janardhanan
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Kaiwalya S
authors.initials: KS
authors.lastname: Deo
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Cong
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Ophthalmology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Muir
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA Department of Ophthalmology, University of Texas Health Science Center, San Antonio, TX, USA duongt@uthscsa.edu.
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy / Q000379:methods; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*
chemical_list: D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Cerebral blood flow; MRI; arterial spin labeling; cerebrovascular dysfunction; eNOS; hypercapnia