Muscle metaboreflex-induced vasoconstriction in the ischemic active muscle is exaggerated in heart failure.

When oxygen delivery to active muscle is insufficient to meet the metabolic demand during exercise, metabolites accumulate and stimulate skeletal muscle afferents, inducing a reflex increase in blood pressure, termed the muscle metaboreflex. In healthy individuals, muscle metaboreflex activation (MMA) during submaximal exercise increases arterial pressure primarily via an increase in cardiac output (CO), as little peripheral vasoconstriction occurs. This increase in CO partially restores blood flow to ischemic muscle.

Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow.

The muscle metaboreflex and arterial baroreflex regulate arterial pressure through distinct mechanisms. During submaximal exercise muscle metaboreflex activation (MMA) elicits a pressor response virtually solely by increasing cardiac output (CO) while baroreceptor unloading increases mean arterial pressure (MAP) primarily through peripheral vasoconstriction. The interaction between the two reflexes when activated simultaneously has not been well established.

Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension.

Unlabelled: Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex.

Muscle metaboreflex activation during dynamic exercise vasoconstricts ischemic active skeletal muscle.

Metabolite accumulation due to ischemia of active skeletal muscle stimulates group III/IV chemosensitive afferents eliciting reflex increases in arterial blood pressure and sympathetic activity, termed the muscle metaboreflex. We and others have previously demonstrated sympathetically mediated vasoconstriction of coronary, renal, and forelimb vasculatures with muscle metaboreflex activation (MMA). Whether MMA elicits vasoconstriction of the ischemic muscle from which it originates is unknown.

Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension.

During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN).