Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicza 2A, PL 15-089 Białystok, Poland.
Pharmacol Rep. 2011;63(6):1450-9. doi: 10.1016/s1734-1140(11)70709-5.
The Bezold-Jarisch reflex is characterized by a sudden bradycardia associated with hypotension induced by the activation of the vanilloid TRPV1 and serotonin 5-HT(3) 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-HT(3) receptors, respectively. In urethane-anesthetized rats, the rapid iv injection of anandamide (0.6 μmol/kg) or phenylbiguanide (0.03 μmol/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 μmol/kg) and was not modified by the cannabinoid CB(1) receptor antagonist rimonabant (0.1 μmol/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-HT(3) receptor antagonist ondansetron (3 μmol/kg). In conclusion, our results suggest that acute myocardial ischemia augments the Bezold-Jarisch reflex induced via activation of TRPV1 and 5-HT(3) receptors located on sensory vagal nerves in the heart.
贝佐尔德-贾里希反射的特征是，在辣椒素 TRPV1 和血清素 5-HT(3)受体被激活后，突然出现心动过缓和低血压。这种反射与多种健康状况有关，包括心肌梗死。本研究旨在阐明急性实验性心肌缺血对分别作为 TRPV1 和 5-HT(3)受体激动剂的花生四烯酸酰胺和苯并胍引发的反射性心动过缓的影响。在乌拉坦麻醉的大鼠中，快速静脉注射花生四烯酸酰胺（0.6 μmol/kg）或苯并胍（0.03 μmol/kg）可使心率（HR）降低约基础值的 7-10%。通过结扎左前冠状动脉诱导心肌缺血（MI）。激动剂在 MI 前 5 分钟（S(1)）和之后 10、20 和 30 分钟（S(2)-S(4)）注射。MI 在 S(2)时使花生四烯酸酰胺引起的反射性心动过缓增强约 105%，在 S(3)时增强约 70%，但在 S(4)时无影响。MI 的这种放大作用几乎被 TRPV1 受体拮抗剂辣椒素（1 μmol/kg）消除，并且不受大麻素 CB(1)受体拮抗剂利莫那班（0.1 μmol/kg）的影响。MI 还使苯并胍引起的反射性心动过缓增强约 110%、60%和 90%（S(2)、S(3)和 S(4)），这种作用对 5-HT(3)受体拮抗剂昂丹司琼（3 μmol/kg）敏感。总之，我们的结果表明，急性心肌缺血增强了通过激活位于心脏感觉迷走神经上的 TRPV1 和 5-HT(3)受体引发的贝佐尔德-贾里希反射。
