Treatment of Hypertensive Obese Zucker Rats with Metformin Enhances Phenylephrine-Induced Bradycardia and c-Fos Expression in the NTS

With the progression of metabolic syndrome adult obese Zucker rats (OZR) develop impaired baroreflexes that coincide with a reduced ability to activate the nucleus tractus solitarius (NTS). The NTS, which receives baroreceptor afferent inputs, appears to respond less to acute rises in mean arterial pressure (MAP) as suggested by less phenylephrine (PE)-induced c-Fos expression compared to age-matched lean Zucker rats (LZR). In addition microinjection of glutamate into the NTS produces smaller reductions in splanchnic sympathetic nerve activity and MAP in adult OZR versus LZR. We have recently observed that prevention of hypertension improves baroreflexes in OZR, but they are still impaired compared to like-treated LZR. Because hyperglycemia impairs NTS function and baroreflexes in type I diabetic rats, we hypothesized that improvement of glycemia in OZR would also enhance baroreflexes and the ability to activate the NTS. OZR and LZR were treated with metformin (MET; 300 mg/kg/day in drinking water) for 3 weeks (began at 13 weeks of age) and compared to untreated age-matched rats. Blood samples were taken in conscious, unfasted rats at 9-10 am. Compared to untreated OZR, MET-treated OZR had lower blood glucose levels (179±19 vs. 120±8 mg/dl, P