Intrathecal neurotensin is hypotensive, sympathoinhibitory and enhances the baroreflex in anaesthetized rat.
OBJECTIVE
The neuromodulatory effects of the gut-neuropeptide neurotensin on sympathetic vasomotor tone, central respiratory drive and adaptive reflexes in the spinal cord, are not known.


METHODS
Neurotensin (0.5 µM-3 mM) was administered into the intrathecal (i.t.) space at the sixth thoracic spinal cord segment in urethane-anaesthetized, paralysed, vagotomized male Sprague-Dawley rats. Pulsatile arterial pressure, splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, ECG and end-tidal CO(2) were recorded.


RESULTS
Neurotensin caused a dose-related hypotension, sympathoinhibition and bradycardia. The maximum effects were observed at 3000 µM, where the decreases in mean arterial pressure (MAP), heart rate (HR) and sSNA reached -25 mmHg, -26 beats min(-1) and -26% from baseline, respectively. The sympathetic baroreflex was enhanced. Changes in central respiratory drive were characterized by a fall in the amplitude of the phrenic nerve activity. Finally, administration of SR 142948A (5 mM), a potent, selective antagonist at neurotensin receptors, caused a potent hypotension (-35 mmHg), bradycardia (-54 beats min(-1) ) and sympathoinhibition (-44%). A reduction in the amplitude and frequency of the phrenic nerve activity was also observed.


CONCLUSIONS
The data demonstrate that neurotensin plays an important role in the regulation of spinal cardiovascular function, affecting both tone and adaptive reflexes.
Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia.
B
B
Zogovic
P M
PM
Pilowsky
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007278:Injections, Spinal; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013153:Splanchnic Nerves / Q000378:metabolism
D002245:Carbon Dioxide; D009496:Neurotensin