This study investigated the positive inotropic and vasorelaxant activity of DHQ-11, a conjugate of flavonoid dihydroquercetin with isoquinoline alkaloid 1-aryl-6,7-dimethoxy-1,2.3,4-tetrahydroisoquinoline. A study was performed using anterior papillary muscle removed from the left ventricle and thoracic aorta dissected from rats. DHQ-11 produced a concentration-dependent positive inotropic effect which was more potent than their parent compounds alone. The positive inotropic effect of conjugate DHQ-11 was signiûcantly attenuated by the â-adrenoreceptor inhibitor propranolol and L-type Ca2+ channel blocker nifedipine. Also, conjugate DHQ-11 markedly potentiated first post-rest responses indicating that it can modulate Ca2+ loading/release processes in the sarcoplasmic reticulum. These results suggest that positive inotropic effect produced by conjugate DHQ-11 may be mediated through activation of the â-AR/ AC/cAMP/PKA pathway that leads to increased Ca2+ influx and rises in Ca2+ loading/release in the SR, resulting in increased [Ca2+]i and enhanced contraction force. DHQ-11 significantly relaxed both high KCl- and phenylephrine-induced contractions of rat aortic rings which were significantly inhibited by lowering extracellular Ca2+ concentration and in the presence of verapamil. DHQ-11 significantly inhibited phenylephrine-induced contractions in a Ca2+-free medium, in the presence of verapamil. The vasorelaxant effect of the DHQ-11 was significantly reduced by the removal of endothelium and in the presence of L-NAME and methylene blue as well as glibenclamide and TEA. These results suggest that the vasorelaxation produced by conjugate DHQ-11 may be mediated by an endothelium-independent mechanism involving activation of KATP and BKCa channels and inhibition of L-type VDCCs and Ca2+ release from the sarcoplasmic reticulum and endothelium-dependent mechanism through activation of the NO/ sGC/cGMP/PKG signaling pathway resulting in a decrease of intracellular Ca2+ levels. These observations reveal that the conjugate DHQ-11 due to its high positive inotropic and vasorelaxant activity could be a promising compound for the design and development of new drugs for the treatment of heart failure. © 2021 Oriental Scientific Publishing Company. All rights reserved.