Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate

Mazher Mohammed, Christopher J. Madden, Michael C. Andresen, Shaun F. Morrison

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The sympathetic nerve activity (SNA) to brown adipose tissue (BAT) regulates BAT thermogenesis to defend body temperature in cold environments or to produce fever during immune responses. The vagus nerve contains afferents that inhibit the BAT SNA and BAT thermogenesis evoked by skin cooling. We sought to determine whether activation of transient receptor potential vanilloid 1 (TRPV1) channels in the nucleus tractus solitarius (NTS), which are prominently expressed in unmyelinated vagal afferents, would affect coldevoked BAT thermogenesis, cardiovascular parameters, or their vagal afferent-evoked responses. In urethane-chloralose-anesthetized rats, during skin cooling, nanoinjection of the TRPV1-agonist resiniferatoxin in NTS decreased BAT SNA (from 695 ± 195% of baseline during cooling to 103 ± 8% of baseline after resiniferatoxin), BAT temperature (-0.8 ± 0.1°C), expired CO2 (-0.3 ± 0.04%), mean arterial pressure (MAP; -20 ± 5 mmHg), and heart rate (-44 ± 11 beats/min). Pretreatment of NTS with the TRPV1 antagonist capsazepine prevented these resiniferatoxin-mediated effects. Intravenous injection of the TRPV1 agonist dihydrocapsaicin also decreased all the measured variables (except MAP). Bilateral cervical or subdiaphragmatic vagotomy attenuated the decreases in BAT SNA and thermogenesis evoked by nanoinjection of resiniferatoxin in NTS but did not prevent the decreases in BAT SNA and BAT thermogenesis evoked by intravenous dihydrocapsaicin. We conclude that activation of TRPV1 channels in the NTS of vagus nerve intact rats inhibits BAT SNA and decreases BAT metabolism, blood pressure, and heart rate. In contrast, the inhibition of BAT thermogenesis following systemic administration of dihydrocapsaicin does not require vagal afferent activity, consistent with a nonvagal pathway through which systemic TRPV1 agonists can inhibit BAT thermogenesis.

Original languageEnglish (US)
Pages (from-to)R134-R143
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume315
Issue number1
DOIs
StatePublished - Jul 2018

Keywords

  • Dihydrocapsaicin
  • Raphe pallidus
  • Resiniferatoxin
  • Sympathetic nerve activity
  • Thermoregulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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