Vasorelaxant Effect of Alkaloid N-deacetyllappaconitine on Vascular Smooth Muscle

In the pathogenesis of cardiovascular diseases, disruption of Ca²⁺ homeostasis in vascular smooth muscle cells and the dysregulation of vasoregulatory mechanisms are considered decisive factors. In particular, dysfunction of the Ca²⁺ transport systems in the plasma membrane and the sarcoplasmic reticulum, and the resulting imbalance of endothelium-dependent vasoactive and regulatory factors, play a crucial role. The aim of this study is to comprehensively assess the mechanisms of the vasorelaxant effects of the alkaloid N-deacetyllappaconitine on rat aortic rings. The isometric contraction force of the aortic rings was recorded using a Grass-Telefactor FT.03 myograph and analysed with the PowerLab data-acquisition software (ADInstruments). The results showed that the N-deacetyllappaconitine alkaloid exerts a dose-dependent vasorelaxant effect on KCl- and PE-induced aortic contractions. N-deacetyllappaconitine alkaloids reduce intracellular Ca²⁺ levels by inhibiting L-type Ca²⁺ channels in the plasma membrane and by attenuating IP₃ receptor activity. Furthermore, by partially activating KATP channels, it causes membrane hyperpolarisation and, by inhibiting the reverse mode of the Na⁺/Ca²⁺ exchange system, slows the influx of Ca²⁺ ions into the cell. Thus, the relaxant effect of the alkaloid N-deacetyllappaconitine on aortic rings is realised through a number of complex mechanisms. HIGHLIGHTS It was established that the vasorelaxant effect of the alkaloid N-deacetyllappaconitine in rat aortic rings is mediated through several complex mechanisms. The vasorelaxant effect of the alkaloid N-deacetyllappaconitine is primarily mediated via non-endothelial mechanisms and involves inhibition of Ca²⁺ release through L-type Ca²⁺ channels and IP₃ receptors in the sarcoplasmic reticulum. Also, The alkaloid N-deacetyllappaconitine reduces intracellular Ca²⁺ homeostasis by activating the SERCA pump and, to a lesser extent, the KATP channel, as well as inhibiting the reverse mode of the Na⁺/Ca²⁺ exchanger, thereby causing relaxation in vascular smooth muscle.