Are sympathetic fibers supplying blood vessels of skeletal muscle cholinergic and do they cause vasodilation upon stimulation?

Sympathetic Cholinergic Vasodilation in Skeletal Muscle

The statement is partially correct but requires important clarification: while sympathetic cholinergic vasodilator fibers to skeletal muscle exist and have been clearly demonstrated in animals (particularly cats), the evidence for their functional significance in humans remains controversial and limited.

The Animal Evidence

In animal models, sympathetic cholinergic vasodilator fibers to skeletal muscle are well-established:

• Electrical stimulation of the hypothalamic defense area in cats produces profound vasodilation of intramuscular small arteries (50-500 μm diameter) that is abolished by cholinergic blockade or sciatic nerve section, but not by alpha- and beta-adrenergic blockade 1
• These sympathetic cholinergic fibers specifically dilate the small intramuscular arteries, which then increases flow velocity and volume flow in upstream vessels 1
• This vasodilation is part of the "defense reaction" response, characterized by hypertension, tachycardia, and skeletal muscle vasodilation 2

The Human Controversy

The existence of functional sympathetic cholinergic vasodilator fibers in human skeletal muscle remains unproven:

• While circumstantial evidence exists (forearm vasodilation during mental stress is atropine-sensitive and absent after sympathectomy), direct histological evidence for sympathetic cholinergic dilator fibers has never been demonstrated in human muscle 2
• Attempts to record sympathetic dilator nerve traffic in human muscle have failed to demonstrate clear evidence for dilator nerve activity 2
• Many "sympathetic dilator" responses persist after local anesthetic nerve block, suggesting alternative mechanisms 2

The Likely Mechanism in Humans

Current evidence suggests that most "sympathetic dilator" responses in human skeletal muscle are mediated by indirect mechanisms rather than direct cholinergic innervation:

• Skeletal muscle dilator responses to sympathoexcitatory maneuvers in humans appear to be nitric oxide (NO)-dependent 2
• The predominant mechanism is likely adrenaline or local cholinergic mechanisms acting to stimulate NO release from the vascular endothelium, rather than direct sympathetic cholinergic nerve fibers 2

The Dominant Sympathetic Effect: Vasoconstriction

In reality, the primary sympathetic effect on skeletal muscle vasculature is vasoconstriction, not vasodilation:

• All arteries and arterioles in skeletal muscle are constricted by sympathetic stimulation, with maximum response at 8-10 Hz 3
• Fluorescence histochemical studies reveal a network of noradrenergic (not cholinergic) nerve fibers on all arterial vessels 3
• During exercise, muscle perfusion represents a balance between metabolic vasodilation and sympathetic vasoconstriction 4
• Increased sympathetic nerve activity restricts blood flow to active muscles to maintain arterial blood pressure 5

Clinical Context: Heart Failure

The concept becomes even more complex in pathological states:

• In heart failure, peripheral vasodilatory capacity is impaired due to excessive sympathetic stimulation, renin-angiotensin activation, and elevated endothelin levels causing vasoconstriction 6, 7
• Vascular resistance in skeletal muscle fails to decrease normally during exercise in heart failure patients, and sympathetic vasoconstriction is partially responsible for this abnormal response 8

Key Caveats

• The statement conflates animal physiology with human physiology—what is clearly true in cats may not apply to humans
• Even in animals where sympathetic cholinergic vasodilation exists, it is a specialized response (defense reaction) rather than the predominant sympathetic effect
• The normal sympathetic innervation of skeletal muscle vessels is adrenergic and causes vasoconstriction, not vasodilation 3