title: The mitochondrial function of the cerebral vasculature in insulin-resistant Zucker obese rats.
abstract: Little is known about mitochondrial functioning in the cerebral vasculature during insulin resistance (IR). We examined mitochondrial respiration in isolated cerebral arteries of male Zucker obese (ZO) rats and phenotypically normal Zucker lean (ZL) rats using the Seahorse XFe24 analyzer. We investigated mitochondrial morphology in cerebral blood vessels as well as mitochondrial and nonmitochondrial protein expression levels in cerebral arteries and microvessels. We also measured reactive oxygen species (ROS) levels in cerebral microvessels. Under basal conditions, the mitochondrial respiration components (nonmitochondrial respiration, basal respiration, ATP production, proton leak, and spare respiratory capacity) showed similar levels among the ZL and ZO groups with the exception of maximal respiration, which was higher in the ZO group. We examined the role of nitric oxide by measuring mitochondrial respiration following inhibition of nitric oxide synthase with N(ω)-nitro-l-arginine methyl ester (l-NAME) and mitochondrial activation after administration of diazoxide (DZ). Both ZL and ZO groups showed similar responses to these stimuli with minor variations.l-NAME significantly increased the proton leak, and DZ decreased nonmitochondrial respiration in the ZL group. Other components were not affected. Mitochondrial morphology and distribution within vascular smooth muscle and endothelium as well as mitochondrial protein levels were similar in the arteries and microvessels of both groups. Endothelial nitric oxide synthase (eNOS) and ROS levels were increased in cerebral microvessels of the ZO. Our study suggests that mitochondrial function is not significantly altered in the cerebral vasculature of young ZO rats, but increased ROS production might be due to increased eNOS in the cerebral microcirculation during IR.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana imerdzo@tulane.edu.
authors.forename: Ivan
authors.initials: I
authors.lastname: Merdzo
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Rutkai
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Tunde
authors.initials: T
authors.lastname: Tokes
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Venkata N L R
authors.initials: VN
authors.lastname: Sure
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Prasad V G
authors.initials: PV
authors.lastname: Katakam
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration; D002536:Cerebral Arteries / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D052250:Nitric Oxide Synthase Type III
keywords: cerebral microvessels; cerebral vessels; insulin resistance; middle cerebral arteries; mitochondria; mitochondrial respiration; reactive oxygen species