Evidence for cholinergically mediated vasodilation at the beginning of isometric exercise in humans

Vasodilation occurs in the nonexercising forearm at the beginning of isometric handgrip despite activation of sympathetic vasoconstrictor reflexes. The mechanism of this response remains unclear. In 33 normal humans, age 24 +/- 1 years (mean +/- SEM), we measured mean arterial pressure, heart rate, and forearm blood flow (plethysmography) in the nonexercising arm during sustained contralateral isometric handgrip at 30% maximal voluntary contraction. Sympathetic nerve activity to calf muscles (microneurography) was also measured in 15 subjects. Handgrip resulted in increases in arterial pressure from 86 +/- 2 to 97 +/- 3 mm Hg (p less than 0.05). Despite increases in nerve activity to calf muscles from 229 +/- 43 to 337 +/- 66 units (p less than 0.005), which would be expected to produce forearm vasoconstriction, forearm vascular resistance in the contralateral resting arm decreased from 20 +/- 3 to 18 +/- 2 units (p less than 0.05). To determine the mechanism of this vasodilatory influence, additional studies were performed with regional autonomic blockade with intra-arterial administration of atropine (0.8 mg, 10 subjects) or propranolol (2.0 mg, eight subjects) into the nonexercising forearm before contraction. Propranolol and vehicle had no effect on forearm vascular responses in the resting arm during SHG in the other arm. In contrast, atropine blocked the vasodilatory response in the resting arm during contraction (delta forearm vascular resistance during contraction, control = -2.1 +/- 0.6 units; postatropine = +0.2 +/- 0.9 units, p less than 0.05). Atropine did not attenuate the vasodilator response to isoproterenol or the vasoconstrictor response to norepinephrine. We conclude 1) a dissociation exists between sympathetic neural and forearm vascular responses to isometric exercise; 2) the vasodilatory response in the nonexercising forearm is not due to sympathetic withdrawal or beta 2-adrenergic-mediated vasodilation; and 3) this response is mediated primarily by cholinergic mechanisms. These studies provide the first direct evidence for active, cholinergically mediated vasodilation during exercise in humans.