Efeitos da manipulação farmacológica dos receptores canabinóides CB2 na função cardíaca do teleósteo matrinxã, Brycon amazonicus

Abstract

In addition to their known classical effects, such as analgesia and impaired cognition and learning, cannabinoids have also been related to the regulation of cardiovascular responses. CB1 and CB2 cannabinoid receptors are present in several organs, including cardiac tissue. However, the effects of activation of these receptors on cardiac contractility are still unclear. The aim of this study was to evaluate ventricular myocardial responses after activation of the CB2 cannabinoid receptor, using fish as an experimental model, which is an attractive tool for testing with innovative therapies. The effects of cb2 receptor activation with a synthetic selective agonist (HU-308) on the contractility of the isolated ventricular myocardium and on the expression of proteins involved with Ca2+ management during excitation-contraction coupling (E-C coupling) were investigated. Treatment with the CB2 receptor agonist increased the contraction force (Fc), cardiac pumping capacity (CPC), besides the contraction and relaxation rates of ventricular strips. Pharmacological manipulations with rianodine (sarcoplasmic reticulum blockade) and lithium (Na+/Ca2+ exchanger blockade) indicated a relevant contribution of both the SR and the Na+/Ca2+ exchanger in E-C coupling in the HU-308 treated group. Furthermore, the treatment with HU-308 induced significant increases in the expression of Na+/Ca2+ exchanger (NCX) (159%), sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) (28%) e phospholamban (PLB) (67%) in the ventricles of matrinxã. In conclusion, CB2 receptors activation improved E-C coupling by increasing calcium-handling efficiency leading to a positive inotropic and lusitropic responses. The beneficial effects observed in this study on myocardial contractility suggest that CB2 receptors may be potential therapeutic targets in cardiac dysfunctions.