Cardiovascular pharmacology of sinomenine: the mechanical and electropharmacological actions.

Sinomenine is one of the alkaloids extracted from Chinese medical plant, Sinomenium acutum Rehder et Wilson. Sinomenine has been used for Rheumatoid arthritis as an anti-inflammatory and immunomodulative drugs. We have so far been investigated the cardiovascular pharmacological actions of sinomenine. Sinomenine dilated NE (5 μM)-, KCl (60 mM)- and PDB (300 nM)-induced vasoconstrictions. The pretreatment with nicardipine (0.1 μM), staurosporine (30 nM), L-NMMA (100 μM), indomethacin (10 μM) or propranolol significantly attenuated the sinomenine-induced vasorelaxation. Therefore, these results indicate that sinomenine causes the vasorelaxation by the involvement with the inhibitions of Ca(2+) current (I(Ca)) and PK-C, β-adrenoceptor stimulation, and the activation of NO and PGI(2) syntheses in endothelium. On the other hand, in the ventricular cardiomyocytes of guinea pig, sinomenine inhibits I(Ca) and simultaneously decreases the delayed rectifier K(+) current (I(K)), resulting in the prolongation of action potential duration. Sinomenine also suppresses the dysrhysmias induced by triggered activities under the Ca(2+) overload condition. Therefore, sinomenine may be expected as one of effective therapeutic drugs for heart failure and dysrhythmias, and may maintain the cardiovascular functions due to modulation of cardiac ionic channels and blood vessels.