Functional sympatholysis in hypertension

• Sympathetic vasoconstriction normally is reduced in active skeletal muscle.
• Termed functional sympatholysis, this local modulation optimizes muscle blood flow.
• Hypertensive animals and humans demonstrate impaired functional sympatholysis.
• The mechanism involves angiotensin II, oxidative stress, and reduced nitric oxide.
• Sympatholysis is restored by select antihypertensive drugs or exercise training.

Sympathetic vasoconstriction is normally attenuated in exercising muscle by local changes in muscle metabolites and other substances that reduce vascular responsiveness to α-adrenergic receptor activation. Termed functional sympatholysis, this protective mechanism is thought to optimize muscle blood flow distribution to match perfusion with metabolic demand. Emerging evidence from both animal and human studies indicate that functional sympatholysis is impaired in hypertension and may constitute an important underlying cause of skeletal muscle malperfusion during exercise in this common cardiovascular condition. Findings from studies of animal models of hypertension and patients with essential hypertension will be integrated in this review to provide insight into the underlying mechanisms responsible for inappropriate sympathetic vasoconstriction in exercising muscle and the treatment options that may restore functional sympatholysis and improve muscle perfusion during exercise.