Exaggerated increases in blood pressure during isometric muscle contraction in hypertension: Role for purinergic receptors

• The pressor response to exercise is exaggerated in hypertension and is mediated, in part, by an overactive skeletal muscle metaboreflex.
• Purinergic receptors contribute to activation of the muscle metaboreflex during muscle contraction.
• Purinergic receptor activation appears to play a modest role in mediating exaggerated metaboreflex function in hypertensive humans.

Physical activity is a cornerstone therapy for the primary prevention and treatment of hypertension, which is becoming increasingly prevalent in modern societies. During exercise, heart rate and blood pressure (BP) increase in order to acutely meet the metabolic demands of the working skeletal muscle. In hypertensive adults, isometric exercise-induced increases in BP are excessive, potentially increasing the risk of an acute cardiovascular event during or after physical activity. Recently, the skeletal muscle metaboreflex has emerged as a significant contributor to the development of aberrant cardiovascular control during isometric exercise in this clinical population. Our laboratory has conducted a series of studies characterizing the skeletal muscle metaboreflex in hypertensive humans. We and others have demonstrated that hypertension is characterized by greater increases in muscle sympathetic nerve activity and BP during selective activation of the metaboreflex during post-exercise muscle ischemia compared to the increases noted in healthy age-matched normotensive adults, suggesting that the skeletal muscle metaboreflex is exaggerated in human hypertension. The focus of this review is the skeletal muscle metaboreflex (i.e., the metabolic component of the exercise pressor reflex) in hypertension, with particular emphasis on the potential role of purinergic receptors in mediating the exaggerated responses to muscle metaboreflex activation.