Exaggerated exercise pressor reflex in type 2 diabetes: Potential role of oxidative stress.

Abstract

Type 2 diabetes mellitus (T2DM) leads to exaggerated cardiovascular responses to exercise, in part due to an exaggerated exercise pressor reflex. Accumulating data suggest excessive oxidative stress contributes to an exaggerated exercise pressor reflex in cardiovascular-related diseases. Excessive oxidative stress is also a primary underlying mechanism for the development and progression of T2DM. However, whether oxidative stress plays a role in mediating the exaggerated exercise pressor reflex in T2DM is not known. Therefore, this review explores the potential role of oxidative stress leading to increased activation of the afferent arm of the exercise pressor reflex. Several lines of evidence support direct and indirect effects of oxidative stress on the exercise pressor reflex. For example, intramuscular ROS may directly and indirectly (by attenuating contracting muscle blood flow) increase group III and IV afferent activity. Oxidative stress is a primary underlying mechanism for the development of neuropathic pain, which in turn is associated with increased group III and IV afferent activity. These are the same type of afferents that evoke muscle pain and the exercise pressor reflex. Furthermore, oxidative stress-induced release of inflammatory mediators may modulate afferent activity. Collectively, these alterations may result in a positive feedback loop that further amplifies the exercise pressor reflex. An exaggerated reflex increases the risk of adverse cardiovascular events. Thus, identifying the contribution of oxidative stress could provide a potential therapeutic target to reduce this risk in T2DM.