Figure 1.

Norepinephrine release in the sympathetic synapse. Vesicular release is stimulated by Ca²⁺ and inhibited by α₂AR. The re-uptake of norepinephrine through NET can be reversed to release by tyramine. Then NET will be engaged in release and re-uptake is hampered, and overflow to plasma is increased. However, vesicular norepinephrine release is not directly influenced by this process, and will still be subjected to presynaptic control by the α₂AR or other presynaptic receptors. Clonidine will lower the sympathetic tone through a central action, as well as stimulate presynaptic and postsynaptic α₂AR. L-659,066, which does not cross the blood-brain barrier, will inhibit the peripheral pre- and postsynaptic α₂AR. In the VSMC, L-659,066 will allow βAR-G_s-signaling to dominate tension control when norepinephrine release is stimulated. Blunted arrows indicate inhibition.