Abstract
<jats:p>Cardiovascular diseases are among the leading causes of death worldwide, according to the World Health Organization. A key pathogenic factor in ischemia and myocardial infarction is the disruption of Ca²⁺ ion homeostasis and impaired function of the sarcoplasmic reticulum (SR) proteins RyR2 and SERCA2a. Therefore, identifying biologically active substances that modulate Ca²⁺ transport via SERCA2a is of significant scientific and practical importance. In this study, the inotropic effects of the isoquinoline alkaloid F-4, the flavonoid dihydroquercetin (DHQ), and their conjugate DKV-6 were investigated using isolated rat heart papillary muscle preparations. Mechanographic results showed that F-4 (120 μM), DHQ (60 μM), and DKV-6 (50 μM) increased papillary muscle contractility by 32.9±3.1%, 51.4±3.4%, and 110.3±3.2%, respectively, compared to control. The post-rest potentiation (PRP) method was employed to assess changes in SR Ca²⁺ levels. The effects of these biologically active compounds (BACs) on RyR2 were studied using tetracaine and ruthenium red, while the role of SERCA2a was evaluated with cyclopiazonic acid (CPA). The results indicated that the positive inotropic effect is closely associated with SERCA2a function. Furthermore, the DKV-6 conjugate exhibits distinct anti-hypoxic activity, effectively counteracting hypoxia-induced impairments in myocardial contractility. Its antiarrhythmic effect appears to be mediated through SERCA2a activation.</jats:p>