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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Teófilo TM,Duarte GP,Borges RS,Santos AA,Magalhães PJC,Lahlou Sdoi
10.1016/j.ejphar.2019.01.063subject
Has Abstractpub_date
2019-04-15 00:00:00pages
154-159eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30081-0journal_volume
849pub_type
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