The Novel Analogue of Hirsutine as an Anti-Hypertension and Vasodilatary Agent Both In Vitro and In Vivo

In this paper, an analogue of hirsutine (compound 1) has been synthesized and evaluated as an anti-hypertension agent, which exhibits extraordinary effects on the contractile response of thoracic aorta rings from male SD rats in vitro (IC₅₀ = 1.129×10^-9±0.5025) and the abilities of reducing the systolic blood pressure (SBP) and heart rate (HR) of SHR in vivo. The mechanism investigation reveals that the vasodilatation induced by compound 1 is mediated by both endothelium-dependent and -independent manners. The relaxation in endothelium-intact aortic rings induced by compound 1 can be inhibited by L-NAME (1×10^-6 mol•L^-1) and ODQ (1×10^-6 mol•L^-1). Moreover, compound 1 can also block Ca²⁺ influx through L-type Ca²⁺ channels and inhibit intracellular Ca²⁺ release while no effect on K⁺ channel has been observed. All these data demonstrated that the NO/cyclic GMP pathway can be involved in endothelium-dependent manner induced by compound 1. Meanwhile the mechanism on the vasodilatation of compound 1 probably also related to blockade of Ca²⁺ influx through L-type Ca²⁺ channels and inhibition of intracellular Ca²⁺ release may have no relationship with K⁺ channels.