Spinal cord injury alters purinergic neurotransmission to mesenteric arteries in rats

Abstract

Complications associated with spinal cord injury (SCI) result from unregulated reflexes below the lesion level. Understanding neurotransmission distal to the SCI could improve quality of life by mitigating complications. The long-term impact of SCI on neurovascular transmission is poorly understood, but reduced sympathetic activity below the site of SCI enhances arterial neurotransmission (1). We studied sympathetic neurovascular transmission using a rat model of long-term paraplegia (T2–3) and tetraplegia (C6–7). Sixteen weeks after SCI, T2–3 and C6–7 rats had lower blood pressure (BP) than sham rats (103 ± 2 and 97 ± 4 vs. 117 ± 6 mmHg, P < 0.05). T2–3 rats had tachycardia (410 ± 6 beats/min), and C6–7 rats had bradycardia (299 ± 10 beats/min) compared with intact rats (321 ± 4 beats/min, P < 0.05). Purinergic excitatory junction potentials (EJPs) were measured in mesenteric arteries (MA) using microlectrodes, and norepinephrine (NE) release was measured using amperometry. NE release was similar in all groups, while EJP frequency-response curves from T2–3 and C6–7 rats were left-shifted vs. sham rats. EJPs in T2–3 and C6–7 rats showed facilitation followed by run-down during stimulation trains (10 Hz, 50 stimuli). MA reactivity to exogenous NE and ATP was similar in all rats. In T2–3 and C6–7 rats, NE content was increased in left cardiac ventricles compared with intact rats, but was not changed in MA, kidney, or spleen. Our data indicate that peripheral purinergic, but not adrenergic, neurotransmission increases following SCI via enhanced ATP release from periarterial nerves. Sympathetic BP support is reduced after SCI, but improving neurotransmitter release might maintain cardiovascular stability in individuals living with SCI. NEW & NOTEWORTHY This study revealed increased purinergic, but not noradrenergic, neurotransmission to mesenteric arteries in rats with spinal cord injury (SCI). An increased releasable pool of ATP in periarterial sympathetic nerves may contribute to autonomic dysreflexia following SCI, suggesting that purinergic neurotransmission may be a therapeutic target for maintaining stable blood pressure in individuals living with SCI. The selective increase in ATP release suggests that ATP and norepinephrine may be stored in separate synaptic vesicles in periarterial sympathetic varicosities.

NPC transplantation rescues sci-driven cAMP/EPAC2 alterations, leading to neuroprotection and microglial modulation

“…These functions include the "Adenosine Receptor signalling pathway" (GO:0,060,167) and "G-protein coupled glutamate receptor signalling" (GO:0,007,216). The alteration of these functions may result from the deleteriously high concentrations of ATP [ 35 ] and glutamate [ 36 ] associated with SCI, which ultimately derive from cell disruption. The upregulation of these functions suggests that these molecules can trigger secondary signalling pathways within the post-injury tissue to induce excitotoxicity by binding to their respective receptors [ 37 ].…”

An Electrochemical ATP Biosensor with Enzymes Entrapped within a PEDOT Film

“…One of our target applications for the biosensor is the in vitro measurement of ATP release from sympathetic nerves supplying blood vessels. Sympathetic nerves release both ATP and norepinephrine (NE) with both functioning as vasoconstrictors to regulate vascular tone [1–4, 16]. Therefore, for this application, it is important to know if the biosensor responds to NE.…”

“…ATP is a key neurosignaling molecule in the vasculature and the gastrointestinal tract [1–5]. For example, sympathetic nerves supplying blood vessels communicate with surrounding smooth muscle cells using norepinephrine and ATP [1–4]. In the gut, ATP functions as an inhibitory neuromuscular signaling molecule [5–7].…”