Neuronal and non-neuronal modulation of sympathetic neurovascular transmission

Abstract

Norepinephrine, 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 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.

Purinergic Signaling and Blood Vessels in Health and Disease

“…In many arteries, the mechanical and electrical responses to perivascular sympathetic nerve stimulation are partially resistant to a-adrenoceptor antagonists. Many reports of sympathetic purinergic excitatory cotransmission to various blood vessels are available, although there is considerable variation in the proportions of ATP and NA used (Burnstock, 1988(Burnstock, , 1990b(Burnstock, , 1995Ralevic and Burnstock, 1998;Hill et al, 2001;Lewis and Evans, 2001;Ralevic, 2009;Macarthur et al, 2011). There appear to be separate stores of NA and ATP in sympathetic nerve terminals, because N and P/Q type calcium channels control NA release, whereas only N-type channels control ATP release (Demel et al, 2010; see also Ellis and Burnstock, 1989).…”

Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1 and CB2 Cannabinoid Receptors

“…For instance, adenosine-triphosphate (ATP) released from sympathetic neurons induces contraction of vascular smooth muscle in a variety of tissues (i.e., vas deferens, aorta, splenic nerve) through the P2X receptor (Sedaa et al 1990;Ren and Burnstock 1997;Burnstock and Ralevic 2014). Extracellular ATP is quickly converted to adenosine, which binds to pre-synaptic A1 adenosine receptors (Kubo and Su 1983;Wennmalm et al 1988;von Kugelgen et al 1992;Rongen et al 1996;Ralevic 2009;Macarthur et al 2011;Burnstock and Ralevic 2014). Activation of A1 adenosine receptors stimulates vascular smooth muscle contraction in the spleen (Fozard and Milavec-Krizman 1993;Tawfik et al 2005).…”

Blunted cerebral blood flow velocity in response to a nitric oxide donor in postural tachycardia syndrome

“…This is of interest as NO from neuronal NO synthase is believed to interact with central ANG II in the regulation of central sympathetic outflow (27), in the myogenic response of cerebral autoregulation (15), and with nitergic interneurons, which participate in the functional hyperemia of the neurovascular coupling (11).…”