Stimulation of pulmonary vagal C-fibers by trans-4-methyl-β-nitrostyrene induces bradycardiac and depressor reflex in rats: Role of vanilloid TRPV1 receptors.

Abstract

Previously, we showed that the synthetic nitroderivative trans-4-methyl-β-nitrostyrene (T4MeN) induced vasorelaxant effects in rat isolated aortic rings. Here, we investigated the mechanisms underlying the cardiovascular effects of T4MeN in normotensive rats. In pentobarbital-anesthetized rats, intravenous (i.v.) injection of T4MeN (0.03-0.5 mg/kg) induced a rapid (onset time of 1-2 s) and dose-dependent bradycardia and hypotension. These cardiovascular responses to T4MeN were abolished by bilateral cervical vagotomy or selective blockade of neural conduction of vagal C-fiber afferents by perineural treatment of both cervical vagus nerves with capsaicin. Hypotension and bradycardia were also recorded when T4MeN was directly injected in the right, but not into the left ventricle. Furthermore, they were significantly reduced by i.v. pretreatment with capsazepine but remained unaltered by ondansetron or suramin. In conscious rats, the dose-dependent hypotension and bradycardia evoked by T4MeN were abolished by i.v. methylatropine pretreatment. In conclusion, bradycardiac and depressor responses induced by T4MeN has a vago-vagal reflex origin resulting from the vagal pulmonary afferents stimulation. The transduction mechanism seems to involve the activation of vanilloid TRPV1, but not purinergic (P2X) or 5-HT3 receptors located on vagal pulmonary sensory nerves.

• Authors: Taylena Maria Teófilo, Glória Pinto Duarte, Rosivaldo Santos Borges, Armênio Aguiar Santos, Pedro Jorge Caldas Magalhães, Saad Lahlou
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 849 Pg. 154-159 (Apr 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30716310 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• 4-methoxy-beta-nitrostyrene
• Styrenes
• TRPV Cation Channels
• TRPV1 receptor

Topics

• Animals
• Bradycardia (chemically induced, metabolism, physiopathology)
• Lung (innervation)
• Male
• Nerve Fibers, Unmyelinated (drug effects, metabolism, physiology)
• Rats
• Rats, Wistar
• Reflex (drug effects)
• Styrenes (pharmacology)
• TRPV Cation Channels (metabolism)
• Vagus Nerve (drug effects)