BACKGROUND Spinal sympathetic preganglionic neurons (SPN) regulate an extensive range of effectors including the pineal and thyroid glands as well cardiovascular and thermoregulatory organs including the heart, the vasculature and brown adipose tissue (BAT). SPN are intrinsically silent but receive substantial input from supraspinal sources, ranging from fast amino acid to slow peptidergic neurotransmitters. Our aim was to determine the role somatostatin has in regulating cardiovascular and thermoregulatory function in the spinal cord.
METHODS & RESULTS Anatomical data shows that the midline raphe nuclei provide about 75% of the preprosomatostatinergic input to the spinal cord. Intrathecal neuronostatin at the T2-T6 spinal level, in urethane-anaesthetised, vagotomised, paralysed rats had no effect. In contrast, somatostatin inhibited select autonomic outflows including HR (-41±6 bpm) and under conditions where iBAT temperature was elevated a fall of about 0.4°C, consistently accompanied by a decrease in expired CO2with very modest effects on MAP (8±1mmHg) or sympathetic nerve activity (SNA 15±3.8%). Very similar effects were evoked using sst2 selective agonists. Surprisingly, selective blockade of sst2 receptors using low doses of BIM-23627 consistently evoked increases in HR (43± 4bpm) and iBAT temperature (1.3±0.2°C) with little effect on other parameters. At higher doses a dose dependent biphasic response was evoked in all parameters except iBAT temperature. This culminated in robust decreases in MAP of ~24 mmHg and SNA (76±4%) which then recovered within ~60 minutes. Further anatomical data reveals the distribution of sst2 receptors in the spinal cord.
CONCLUSIONS These findings indicate that in the spinal cord 1) SST evokes select autonomic effects mediated via sst2 receptors 2) sst2 receptors are tonically activated particularly with respect to iBAT and heart rate control. This suggests that neuroinhibitory peptides may be tonically secreted within the spinal cord. One source of this peptide may be the midline raphe.
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