Altered respiratory response to substance P in capsaicin-treated rats

✍ Scribed by A. C. Towle; R. A. Mueller; G. R. Breese; J. Lauder

• Publisher: John Wiley and Sons
• Year: 1985
• Tongue: English
• Weight: 896 KB
• Volume: 14
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490140209

✦ Synopsis

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothaneanesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaC02 equal to and PaOz greater than vehicle injected controls. In addition, the minute ventilation-PaC02 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaC02 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent.

The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaC02 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaC02 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin.

Thcsc results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.