Aortic vasorelaxation is not blunted in female Zucker diabetic fatty rats and is unaltered by anti‐diabetic metformin treatment, chronic exercise training, or a combination of both

Abstract

Male (m) Zucker diabetic fatty rats (ZDF) exhibit severely impaired endothelium‐dependent vasorelaxation (EDR) but responses in female (f) ZDF are unknown. fZDF (6 wk old, n=66) received 8 wk of: A. standard non‐diabetogenic chow (16.7 % kcal from fat) with no intervention and were lean (Lean, +/?, 188±3 g) or obese (Con, fa/fa, 358±6 g); or B. high‐fat diabetogenic chow (48 % kcal from fat, all fa/fa) with either no intervention (HF, 345±8 g), anti‐diabetic metformin treatment (HF‐Met, up to 500 mg/kg/d, 350±7 g), chronic exercise training (HF‐Ex, up to 2 h/d, 18–19 m/min, 10 % grade, 5 d/wk, 339±3 g), or Met and Ex (HF‐E+M, 337±4 g). In vitro thoracic aortic EDR (acetylcholine, 10−10−10−4 M) was assessed in the absence (ND) or presence of a superoxide dismutase mimetic (Tempol, 10−4 M). All fa/fa groups were obese and hyperinsulinemic vs. Lean (p<0.05). Hyperglycemia induced in HF was abrogated by all interventions (p<0.05). EDR was equal and unimpaired in all groups in the ND condition. Tempol elevated EDR in HF‐Ex (vs. ND, p<0.05), but did not affect any other groups. In this first report of vasomotor function in fZDF, responses were unaffected by severe obesity and diabetic‐like symptoms and unaltered by Met and/or Ex treatment. These data contrast the severely impaired EDR in mZDF. Mechanism(s) responsible for the apparent sex‐dependent vasculoprotection in fZDF is presently unclear. Funded by HSF Canada, NSERC, and CIHR.