Muscarinic actions of acetylcholine on the heart, vessels and smooth muscle
THE CONTEXT
Acetylcholine slows cardiac activity, generally dilates vessels through the endothelium, and contracts smooth muscle in several organs.
Cardiac effects
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Acetylcholine hyperpolarizes sinoatrial nodal cells and reduces the rate of diastolic depolarization, producing bradycardia or even cardiac arrest.
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At the atrioventricular node and His–Purkinje fibres, the refractory period increases and conduction slows. The P–R interval increases, and partial or complete atrioventricular block may occur.
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Atrial contractile force decreases markedly, while the atrial refractory period is shortened.
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Nonuniform vagal innervation creates differences in atrial conduction and refractory periods, predisposing to atrial fibrillation or flutter.
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Ventricular contractility decreases less markedly. Cardiac muscarinic receptors are M2 receptors.
Vascular effects
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Acetylcholine dilates blood vessels, causing a fall in blood pressure and flushing, especially in the blush area.
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Vascular endothelial M3 receptors mediate vasodilatation primarily through release of nitric oxide, the endothelium-dependent relaxing factor.
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When endothelium is damaged, acetylcholine can reach vascular smooth muscle and cause vasoconstriction through smooth muscle M3 receptors.
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Cholinergic stimulation of the penis promotes erection through nitric oxide release and cavernosal vessel dilatation involving M3 receptors. This response is minimal with injected cholinomimetic drugs.
Gastrointestinal, urinary and bronchial effects
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Smooth muscle in most organs contracts mainly through M3 receptors. Gastrointestinal tone and peristalsis increase while sphincters relax, producing abdominal cramps and bowel evacuation.
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Ureteric peristalsis increases. Detrusor contraction with relaxation of the bladder trigone and sphincter promotes bladder voiding.
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Bronchial smooth muscle constricts. Asthmatic patients are highly sensitive and may develop bronchospasm, dyspnoea or an asthma attack.