Neuronal and non-neuronal modulation of sympathetic neurovascular transmission

Abstract

Noradrenaline, neuropeptide Y and adenosine triphosphate are co-stored in, and co-released from, sympathetic nerves. Each transmitter modulates its own release as well as the release of one another; thus, anything affecting the release of one of these transmitters has consequences for all. Neurotransmission at the sympathetic neurovascular junction is also modulated by non-sympathetic mediators such as angiotensin II, serotonin, histamine, endothelin and prostaglandins through the activation of specific pre-junctional receptors. In addition, nitric oxide (NO) has been identified as a modulator of sympathetic neuronal activity, both as a physiological antagonist against the vasoconstrictor actions of the sympathetic neurotransmitters, and also by directly affecting transmitter release. Here, we review the modulation of sympathetic neurovascular transmission by neuronal and non-neuronal mediators with an emphasis on the actions of NO. The consequences for co-transmission are also discussed, particularly in light of hypertensive states where NO availability is diminished.

Schema 1

Schema depicts co-transmission of norepinephrine (NE), neuropeptide Y (NPY) and adenosine triphosphate (ATP) at the sympathetic neurovascular junction.

Schema 2

A) Schema depicts the modulation exerted by nitric oxide (NO) on the norepinephrine (NE) portion of sympathetic neurotransmission under normal conditions. NO, produced in the endothelial cell from L-Arginine, diffuses to the vascular smooth muscle where it activates soluble guanylate cyclase (sGC) leading to an increase in cGMP and vasorelaxation. NO further diffuses into the neurovascular junction where it reacts with, and deactivates, NE, thus placing a “brake” on the post and pre-junctional activity of NE. As a consequence neuropeptide Y (NPY) release is enhanced. The effect on adenosine triphosphate (ATP) is unknown. B) Schema depicts how NO-induced modulation of NE alters during developing hypertension. Increased superoxide (O₂⁻) production within the vascular smooth muscle limits the activity of NO and thus limits the amount of NO that diffuses to the sympathetic neurovascular junction. The presence of less NO effectively removes the “brake” on the activity of NE resulting in enhanced NE-induced post-junctional vasoconstriction and pre-junctional inhibition of NPY release. The effect on ATP is unknown.