Adrenergic neuroeffector interaction in the blood vessel wall

Abstract

Most blood vessels are supplied with adrenergic nerve fibers, which in their varicosities contain vesicles formed in the neuron cell body. The vesicles are the storage sites for norephinephrine, whether synthesized locally from tyrosine or actively taken up from the extracellular fluid by the varicosities (neuronal uptake). Norepinephrine can leave the storage sites 1) by leakage into the neuroplasm, in which case most of it is metabolized intraneuronally by monoamine oxidase; 2) by displacement with indirect sympathomimetic amines; and 3) by active release, together with dopamine-β-hydroxylase, the enzyme catalyzing the final step of the norepinephrine synthesis: this exocytotic process is triggered by an increase in neuroplasmic Ca2+ concentration resulting from neuronal membrane depolarization. The norepinephrine released into the junctional cleft from the adrenergic varicosity diffuses to the smooth muscle cells where it binds to receptor or acceptor sites on the membrane. The binding to the receptors initiates a change in the activity of the vascular smooth muscle; in most vessels the norepinephrine-receptor interaction is alpha-adrenergic and evokes a constriction. Released norepinephrine is removed by 1) neuronal uptake, 2) overflow to the extracellular fluid and the bloodstream, 3) binding to nonvascular smooth muscle structures, and 4) uptake by smooth muscle cells and subsequent metabolization by catechol-O-methyl transferase and monoamine oxidase; the relative importance of these different deactivation pathways depends mainly on anatomical factors such as density and pattern of innervation.