Intrathecal neurotensin is hypotensive, sympathoinhibitory and enhances the baroreflex in anaesthetized rat.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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.

KEY 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 AND IMPLICATIONS:

The data demonstrate that neurotensin plays an important role in the regulation of spinal cardiovascular function, affecting both tone and adaptive reflexes.

• Authors: B Zogovic, P M Pilowsky
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 166 Issue 1 Pg. 378-89 (May 2012) ISSN: 1476-5381 [Electronic] England
• PMID: 22035146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Carbon Dioxide
• Neurotensin

Topics

• Animals
• Baroreflex (drug effects)
• Blood Pressure (drug effects)
• Bradycardia (chemically induced)
• Carbon Dioxide (metabolism)
• Dose-Response Relationship, Drug
• Electrocardiography
• Heart Rate (drug effects)
• Hypotension (chemically induced)
• Injections, Spinal
• Male
• Neurotensin (administration & dosage, metabolism, pharmacology)
• Phrenic Nerve (metabolism)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (drug effects, metabolism)
• Splanchnic Nerves (metabolism)