Trigeminocardiac reflex by mandibular extension on rat pial microcirculation: role of nitric oxide

PLoS One. 2014 Dec 31;9(12):e115767. doi: 10.1371/journal.pone.0115767. eCollection 2014.


In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / physiology*
  • Cerebral Veins / physiology*
  • Heart Rate / physiology*
  • Male
  • Mandible / blood supply
  • Mandible / surgery*
  • Microcirculation
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis
  • Nociceptors / physiology
  • Rats
  • Rats, Wistar
  • Reflex, Trigeminocardiac / drug effects
  • Reflex, Trigeminocardiac / physiology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Narcotic Antagonists
  • Nitric Oxide
  • Naloxone
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester

Grants and funding

This work was supported by a grant from ATENEO Pisa, 2013–14. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.