Mechanism of Vasorelaxant Action of Isoquinoline Alkaloid F-19 on Rat Aorta
Abstract
The development of cardiovascular diseases is primarily associated with impaired activity of ion transport systems that ensure Ca2+ homeostasis in vascular smooth muscle cells. Modulation of the function of Ca2+ ion transport systems in smooth muscle cells with biologically active compounds allows the development of new approaches to the pharmacological regulation of Ca2+-dependent processes in cardiovascular diseases. This article studies the mechanisms of the vasorelaxant effect of the isoquinoline alkaloid 1-(3¢-Bromo-4¢-hydroxyphenyl-5¢-methoxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (F-19) on the force of aortic ring contraction. It was found that the alkaloid F-19 exerts a concentration-dependent (5-100 μM) potent vasorelaxant effect on the force of aortic ring contraction induced by KCl and PE. The involvement of the L-type Ca2+ channel in the vasorelaxant effect of the alkaloid F-19 was investigated under conditions of incubation with its specific blocker verapamil. It was found that the role of the L-type Ca2+ channel in the vasorelaxant effect of this alkaloid is minor. The effect of the alkaloid F-19 on Ca2+ transport systems in the SR was also investigated. In this case, PE and caffeine-induced transient aortic contraction in the absence of Ca2+ significantly reduced. At the same time, a decrease in the vasorelaxant effect on aortic contractility was observed under the conditions of incubation with the SERCA inhibitor CPA, the alkaloid F-19. The vasorelaxant effect of the alkaloid F-19 on rat aortic smooth muscle contractility is mediated by several complex mechanisms. The vasorelaxant effect of this alkaloid is provided by inhibiting the entry of Ca2+ ions into the cytosol through plasma membrane potential-dependent L-type Ca2+ channels and the exit of Ca2+ ions into the cytosol through the SR Ca2+ transport systems, and by activating SERCA.