{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:22:11Z","timestamp":1790036531110,"version":"4.0.1"},"reference-count":53,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"College of Veterinary Medicine, University of Missouri","award":["Pilot Grant"],"award-info":[{"award-number":["Pilot Grant"]}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["RO1 HL112998"],"award-info":[{"award-number":["RO1 HL112998"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:p> This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism and that 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 to 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 \u2264 0.04). Dilation to insulin was normalized with endothelin-1a receptor antagonism in the OB groups (between groups, P \u2265 0.56), and insulin-stimulated NOS-mediated dilation was greater in the RUN-40 vs. OB-40 group ( P &lt; 0.01). At 40 wk of age, cerebellum BF decreased during EHC in the OB-40 group ( P = 0.02) but not CON or RUN groups ( P \u2265 0.36). Barnes maze testing revealed increased entry errors and latencies in the RUN-40 vs. CON and OB groups ( P &lt; 0.01). These findings indicate that obesity-induced impairments in vasoreactivity to insulin involve increased endothelin-1 and decreased nitric oxide 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. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY The new and noteworthy findings are that 1) in rodents, obesity-related deficits in insulin-mediated vasodilation are associated with increased influence of insulin-stimulated ET-1 and depressed influence of insulin-stimulated NOS and 2) a physical activity intervention, initiated after the onset of disease, restores insulin-mediated vasodilation, likely by normalizing insulin-stimulated ET-1 and NOS balance. These data demonstrate that the treatment effects of chronic exercise on insulin-mediated vasodilation extend beyond active skeletal muscle vasculature and include the cerebrovasculature. <\/jats:p>","DOI":"10.1152\/japplphysiol.00811.2016","type":"journal-article","created":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T20:10:41Z","timestamp":1486671041000},"page":"1040-1050","source":"Crossref","is-referenced-by-count":26,"title":["A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation"],"prefix":"10.1152","volume":"122","author":[{"given":"T. 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