Adrenergic and Cholinergic Receptors in Blood Vessels

Most arteries and veins in the body are innervated by sympathetic adrenergic nerves, which release norepinephrine (NE) as a neurotransmitter. Some blood vessels are innervated by parasympathetic cholinergic or sympathetic cholinergic nerves, both of which release acetylcholine (ACh) as their primary neurotransmitter. Neurotransmitter binding to the adrenergic and cholinergic receptors activates signal transduction pathways that cause the observed changes in vascular function.

NE preferentially binds α₁-adrenoceptors to cause smooth muscle contraction and vasoconstriction. Similar responses occur when NE binds to postjunctional α₂-adrenoceptors located on some blood vessels. NE also binds weakly to postjunctional β₂-adrenoceptors, which causes vasodilation (this can be observed during alpha adrenoceptor blockade), although this vasodilator effect of NE is relatively minor and overwhelmed by alpha adrenoceptor-mediated vasoconstriction. Circulating epinephrine (EPI) binds with high affinity to smooth muscle β₂-adrenoceptors to cause vasodilation in some organs; however, the effect EPI is very concentration dependent. While EPI has a higher affinity for β₂ than postjunctional α₁ or α₂-adrenoceptors, at high concentrations it does bind to the postjunctional α₁ and α₂-adrenoceptors, which can override the vasodilatory effects of β₂-adrenoceptor stimulation and produce vasoconstriction.

Some blood vessels in the body are innervated by parasympathetic cholinergic fibers (e.g., coronary vessels). These nerves release ACh, which binds to muscarinic receptors on the smooth muscle and/or endothelium. In coronary arteries, M₃ receptors on the vascular endothelium are coupled to the formation of nitric oxide (NO), which causes vasodilation; however, ACh causes smooth muscle contraction through a smooth muscle M₃ receptor when formation of NO is blocked. This latter finding has been used to assess coronary vascular dysfunction in humans in which NO production is diminished in diseased coronary arteries. Unlike coronary arteries, cerebral arteries appear to have M₅ muscarinic receptors that produce vasodilation in response to ACh.

Some arterial blood vessels, for example in skeletal muscle, are innervated by sympathetic cholinergic nerves that release ACh and cause vasodilation. This may contribute to active hyperemia in skeletal muscle, particularly at the onset of exercise.

Drugs are available for blocking vascular adrenergic receptors. Alpha-blockers, for example, are used in treating hypertension. Some of the alpha-blockers are relatively selective for a specific receptor subtype, whereas other as non-selective.  Drugs such as atropine block muscarinic receptors.

Revised 02/02/2008