Role of Chronic Stress and Exercise on Microvascular Function in Metabolic Syndrome

Purpose—The present study examined the effect of unpredictable chronic mild stress (UCMS) on peripheral microvessel function in healthy and metabolic syndrome (MetS) rodents, and whether exercise training could prevent the vascular dysfunction associated with UCMS. Methods—Lean and obese (model of MetS) Zucker rats (LZR; OZR) were exposed to 8 weeks of UCMS, exercise (Ex), UCMS+Ex, or control conditions. At the end of the intervention, gracilis arterioles (GAs) were isolated and hung in a pressurized myobath to assess endotheliumdependent (EDD) and -independent (EID) dilation. Levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured through DAF-FM and DHE staining, respectively. Results—Compared to LZR controls, EDD and EID was lower (p=0.0001) in LZR-UCMS. The OZR-Ex group had a higher EDD (p=0.0001) and EID (p=0.003), compared to OZR-Controls; whereas only a difference in EDD (p=0.01) was noted between LZR-Control and LZR-Ex groups. Importantly, EDD and EID were higher in the LZR (p=0.0001; p=0.02) and OZR (p=0.0001; p=0.02) UCMS+Ex groups compared to UCMS alone. Lower NO bioavailability and higher ROS were noted in the LZR-UCMS group (p=0.0001), but not OZR-UCMS, compared to controls. Ex and UCMS-Ex groups had higher NO bioavailability (p=0.0001) compared to control and UCMS groups, but ROS levels remained high. Conclusions—The comorbidity between UCMS and MetS does not exacerbate the effects of one another on GA EDD responses, but does lead to the development of other vasculopathy adaptations, which can be partially explained by alterations in NO and ROS production. Importantly, exercise training alleviates most of the negative effects of UCMS on GA function