Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT3 receptor-mediated Bezold-Jarisch reflex in rats

作者：Lupinski Sebastian L; Schlicker Eberhard; Pedzinska Betiuk Anna; Malinowska Barbara^*

来源：Pharmacological Reports, 2011, 63(6): 1450-1459.

• Bezold-Jarisch reflex
• TRPV1 receptors
• 5-HT3 receptors
• anandamide
• phenylbiguanide
• myocardial ischemia

The Bezold-Jarisch reflex is characterized by a sudden bradycardia associated with hypotension induced by the activation of the vanilloid TRPV1 and serotonin 5-HT3 receptors. This reflex is associated with several health conditions, including myocardial infarction. The aim of the present study was to elucidate the influence of acute experimental myocardial ischemia on the reflex bradycardia induced by anandamide and phenylbiguanide, agonists of the TRPV1 and 5-HT3 receptors, respectively.
In urethane-anesthetized rats, the rapid iv injection of anandamide (0.6 mu mol/kg) or phenylbiguanide (0.031 mu mol/kg) decreased heart rate (HR) by about 7-10% of the basal values. Myocardial ischemia (MI) was induced by ligation of the left anterior coronary artery. The agonists were injected 5 min before MI (S-1) and 10, 20 and 30 min thereafter (S-2-S-4).
MI potentiated the anandamide-induced reflex bradycardia by approximately 105% at S-2 and 70% at S-3 but had no effect at S-4. This amplificatory effect of MI was virtually abolished by the TRPV1 receptor antagonist capsazepine (1 mu mol/kg) and was not modified by the cannabinoid CBI receptor antagonist rimonabant (0.1 mu mol/kg). MI also amplified the reflex bradycardia elicited by phenylbiguanide by approximately 110, 60 and 90% (S-2, S-3 and S-4, respectively), and this effect was sensitive to the 5-HT3 receptor antagonist ondansetron (3 mu mol/kg).
In conclusion, our results suggest that acute myocardial ischemia augments the Bezold-Jarisch reflex induced via activation of TRPV1 and 5-HT3 receptors located on sensory vagal nerves in the heart.

• 出版日期2011-12