This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism, and treatment with a physical activity intervention restores vasoreactivity to insulin through augmented nitric oxide synthase (NOS)-dependent dilation. Otsuka Long-Evans Tokushima Fatty rats were divided into the following groups; 20-wk old food-controlled (CON-20); 20-wk old free-food access (model of obesity, OB-20); 40-wk old food-controlled (CON-40); 40-wk old free-food access (OB-40); and 40-wk old free-food access+RUN (RUN-40; wheel-running access from 20-40 wk). Rats underwent Barnes maze testing and a euglycemic hyperinsulinemic clamp (EHC). In the 40-wk cohort, cerebellum and hippocampus blood flow (BF) were examined (microsphere-infusion). Vasomotor responses (pressurized myography) to insulin were assessed in untreated, endothelin-1a receptor antagonism and NOS inhibition conditions in posterior cerebral arteries. Insulin-stimulated vasodilation was attenuated in the OB vs. CON and RUN groups (P≤0.04). Dilation to insulin was normalized with endothelin-1a receptor antagonism in the OB groups (between groups, P≥0.56) and insulin-stimulated NOS-mediated dilation was greater in the RUN-40 vs. OB-40 group (P<0.01). At 40-wk of age, cerebellum BF decreased during the EHC in the OB-40 group (P=0.02), but not CON or RUN groups (P≥0.36). Barnes maze testing revealed increased entry errors and latencies in the RUN-40 vs. CON and OB groups (P<0.01). These findings indicate OB-induced impairments in vasoreactivity to insulin involve increased endothelin-1 and decreased NO signaling. Chronic spontaneous physical activity, initiated after disease onset, reversed impaired vasodilation to insulin and decreased Barnes maze performance, possibly because of increased exploratory behavior.
- insulin-induced dilation
- physical actvity
- Copyright © 2016, Journal of Applied Physiology