title: Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation between low- and high-intrinsic aerobic capacity rats.
abstract: Low-intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascular dysfunction and impaired vascular reactivity to insulin compared to high capacity running (HCR) rats. Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary conditions, and in vitro thoracic aortic vascular function was assessed. LCR exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal, and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal glucose tolerance test, glucose area under the curve (AUC) was not different but insulin AUC was 2-fold greater in LCR than HCR. Acetylcholine and insulin-stimulated aortic vasorelaxation was significantly greater in LCR (65.2 ± 3.8%, and 32.7 ± 4.1%) than HCR (55.0 ± 3.3%, and 16.7 ± 2.8%). Inhibition of nitric oxide synthase (NOS) with L-NAME entirely abolished insulin-mediated vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited greater expression of Insulin Receptor protein, lower Endothelin Receptor-A protein, a down-regulation of transcripts for markers of immune cell infiltration (CD11C, CD4, and F4/80) and up-regulation of pro-atherogenic inflammatory genes (VCAM-1 and MCP-1) in the aorta wall. Contrary to our hypothesis, low-aerobic capacity was associated with enhanced aortic endothelial function and NO-mediated reactivity to insulin, despite increased adiposity and evidence of whole body insulin resistance.
authors.affiliation: Nutritional Sciences, University of Texas, Austin, Texas jcrissey@austin.utexas.edu.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Crissey
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri Child Health, University of Missouri, Columbia, Missouri.
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Vieira-Potter
authors.affiliation: Biomedical Sciences, University of Missouri, Columbia, Missouri.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Thorne
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Molecular and Integrative Physiology, Kansas University Medical Center, Kansas, Kansas.
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri Biomedical Sciences, University of Missouri, Columbia, Missouri Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri.
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
keywords: Aerobic capacity; nitric oxide; vascular reactivity to insulin