Muscle mechanoreflex overactivity in hypertension: A role for centrally-derived nitric oxide

• The cardiovascular response to exercise is exaggerated in hypertension.
• Skeletal muscle mechanoreflex overactivity mediates this hyper-responsiveness.
• Reflex overactivity occurs due to alterations in brainstem nitroxidergic pathways.
• Alterations include decreased NOS expression and increased oxidative stress.
• Treatment could enhance the safety of exercise prescription in hypertension.

The cardiovascular response to exercise is abnormally large in hypertension. Over the past decade, it has become clear that the exercise pressor reflex (a peripheral feed-back mechanism originating in skeletal muscle) contributes significantly to the generation of this hyper-responsiveness. Further, it has been determined that overactivity of the mechanically (muscle mechanoreflex) and chemically (muscle metaboreflex) sensitive components of the exercise pressor reflex underpin its dysfunction. Given the recent attention in the literature, this review focuses upon the aberrant function of the muscle mechanoreflex in this disease. Evidence supporting a role for the mechanoreflex in the pathogenesis of the exaggerated cardiovascular response to physical activity is highlighted. The peripheral and central mechanisms that may be responsible for mechanoreflex overactivity in hypertension are likewise discussed. Particular attention is given to emerging evidence implicating a role for centrally-derived nitric oxide in this process.