Effects of digoxin on muscle reflexes in normal humans

Blockade of the skeletal muscle Na(+)-K(+)-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V(E)), oxygen saturation (SpO(2)), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V(E), SpO(2), and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na(+)-K(+)-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.