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.
Highlights
We investigated the relationship between intrinsic aerobic exercise capacity and vascular insulin reactivity in a rodent model divergent in endurance running capacity (LCR and high capacity running (HCR) rats) known to display differing metabolic profiles (Noland et al 2007; Lessard et al 2009; Naples et al 2010) by testing the hypothesis that inherited low-aerobic capacity is associated with vascular dysfunction and impaired vasorelaxation
Our main findings include: (1) aortic endothelial dependent vasorelaxation, assessed by ACh, was similar if not greater in low capacity to run (LCR) compared to HCR rats; (2) insulin-stimulated vasorelaxation of the aorta was greater in LCR compared to HCR rats; (3) the contribution of nitric oxide (NO) in mediating insulin-stimulated vasorelaxation was greater in LCR compared to HCR rats; (4) the aorta of LCR rats displayed greater expression of Insulin Receptor (IR) protein and lower vasoconstrictive Endothelin Receptor-A (ETA) receptor protein; and (5) the aorta of LCR rats exhibited increased mRNA expression of VCAM-1 and MCP-1 but decreased mRNA for markers of immune cell infiltration
We chose to assess the influence of intrinsic aerobic capacity on endothelial function, because it has been shown to be an independent predictor of long-term cardiovascular disease progression and cardiovascular events (Schachinger et al 2000)
Summary
We tested the hypothesis that inherited low-aerobic capacity in LCR rats is associated with vascular dysfunction and impaired vasorelaxation to insulin in the aorta. Counter to our hypothesis endothelium dependent dilation, assessed by acetylcholine (ACh)-induced vasorelaxation in thoracic aortic rings was significantly greater in LCR compared to HCR animals (Fig. 5A, Group effect P < 0.05).
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