Acetylcholine [a-se-teel-KOE-leen] is a quaternary ammonium compound that cannot penetrate membranes. Although it is the neurotransmitter of parasympathetic and somatic nerves as well as autonomic ganglia, it is therapeutically of no importance because of its multiplicity of actions and its rapid inactivation by the cholinesterases. Acetylcholine has both muscarinic and nicotinic activity. Its actions include:
1. Decrease in heart rate and cardiac output: The actions of acetylcholine on the heart mimic the effects of vagal stimulation. For example, acetylcholine, if injected intravenously, produces a brief decrease in cardiac rate (negative chronotropy) and stroke volume as a result of a reduction in the rate of firing at the sinoatrial (SA) node. [Note: It should be remembered that normal vagal activity regulates the heart by the release of acetylcholine at the SA node).
2. Decrease in blood pressure: Injection of acetylcholine causes vasodilation and lowering of blood pressure by an indirect mechanism of action. Acetylcholine activates M3 receptors found on endothelial cells lining the smooth muscles of blood vessels. This results in the production of nitric oxide from arginine.3 [Note: nitric oxide is also known as endotheliumderived relaxing factor.] Nitric oxide then diffuses to vascular smooth muscle cells to stimulate protein kinase G production, leading to hyperpolarization and smooth muscle relaxation. In the absence of administered cholinergic agents, the vascular receptors have no known function, because acetylcholine is never released into the blood in any significant quantities. Atropine blocks these muscarinic receptors and prevents acetylcholine from producing vasodilation.
3. Other actions: In the gastrointestinal tract, acetylcholine increases salivary secretion and stimulates intestinal secretions and motility. Bronchiolar secretions are also enhanced. In the genitourinary tract, the tone of the detrusor urinae muscle is increased, causing expulsion of urine. In the eye, acetylcholine is involved in stimulating ciliary muscle contraction for near vision and in the constriction of the pupillae sphincter muscle, causing miosis (marked constriction of the pupil). Acetylcholine (1% solution) is instilled into the anterior chamber of the eye to produce miosis during ophthalmic surgery.