Abstract：
In addition to their well-known classical effects, cannabinoid CB1 and CB2 receptors have also been involvement in both deleterious and protective actions on the heart under various pathological conditions. While the potential therapeutic applications of the endocannabinoid system in the context of cardiovascular function are indeed a viable prospect, significant debate exists within the literature regarding whether CB1, CB2, or a combination of both receptors exert a favorable influence on cardiac function. Hence, the aim of this study was to investigate the effects of CB1 + CB2 or CB2 agonists on cardiac excitation-contraction (E-C) coupling, utilizing fish (Brycon amazonicus) as an experimental model. The CB2 agonist elicited marked positive inotropic and lusitropic responses in isolated ventricular myocardium, induced cyclic adenosine 3\',5\'-monophosphate (cAMP) production, and upregulated critical Ca2+ handling proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). Our current study demonstrated, for the first time, that CB2 receptor activation-induced effects improved the efficiency of Ca2+ cycling, excitation-contraction coupling (E-C coupling), and cardiac performance in under physiological conditions. Hence, CB2 receptors could be considered a potential therapeutic target for modulating cardiac contractile dysfunctions.
摘要：
除了他们众所周知的经典效果，大麻素CB1和CB2受体在各种病理条件下也参与对心脏的有害和保护作用。虽然内源性大麻素系统在心血管功能方面的潜在治疗应用确实是一个可行的前景，关于CB1,CB2或两种受体的组合是否对心脏功能产生有利影响,文献中存在显著的争论.因此，这项研究的目的是研究CB1+CB2或CB2激动剂对心脏兴奋-收缩（E-C）偶联的影响，利用鱼(亚马逊白云)作为实验模型。CB2激动剂在孤立的心室心肌中引起明显的正性肌力和嗜糖反应，诱导环腺苷3'，5'-单磷酸盐（cAMP）生产，并上调关键的Ca2+处理蛋白，例如sarco/内质网Ca2-ATPase（SERCA）和Na/Ca2交换剂（NCX）。我们目前的研究表明，第一次,CB2受体激活诱导的效应提高了Ca2+循环的效率，激励-收缩耦合（E-C耦合），和生理条件下的心脏表现。因此，CB2受体可以被认为是调节心脏收缩功能障碍的潜在治疗靶标。
