Adrenergic and Cholinergic Receptors in Blood Vessels
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. It has been shown in many arterial vessels that 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 receptors (coupled to Gq-proteins and increased IP3) and M2 receptors (coupled to Gi-proteins and decreased cAMP) 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. In contrast to other arteries, cerebral arteries appear to have M5 muscarinic receptors that produce vasodilation in response to ACh.
Some arterial blood vessels in skeletal muscle of dogs and cats (but not humans) are innervated by sympathetic cholinergic nerves that release ACh and cause vasodilation. In species having sympathetic cholinergic nerves, their activation 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.