Flavonoids cyclic nucleotide phosphodiesterase inhibition

Orallo, F., Camifla, M., Alvarez, E., Basaran, H., and Lugnier, C. 2005. Implication of cyclic nucleotide phosphodiesterase inhibition inthe vasorelaxant activity of the Citrus-fruits flavonoid (-)-naringenin ,7 la/ifaMe[Pg.479]

There are several mechanisms involved in the vasodilator effect of flavonoids. The main mechanism seems to be related to the inhibition of protein kinase C or some of the processes activated by this protein. The inhibition of other protein kinases and cyclic nucleotide phosphodiesterase activity and blockage of calcium entry can also contribute to this effect to a greater or lesser extent (Alvarez Castro and Orallo, 2003 Herrera and others 1996). Certain flavonoids, like the flavonol myricetin, have a two-phase action on blood vessels vasoconstrictor in lowest active concentrations and vasodilator in higher concentrations (Alvarez Castro and Orallo, 2003). 

Picq M, Dubois M, Prigent AF, Nemoz G, Pacheco H. 1989. Inhibition of the different cyclic nucleotide phosphodiesterase isoforms separated from rat brain by flavonoid compounds. Biochem Int 18 47-57. 

Some investigators have employed the enhancement of vascular tone in vivo after treatment with these drugs to inhibit amine reuptake where the flavonoids act as antagonists of plasma membrane amine transporters [104]. The vasodilatory mechanism of flavonoids seems to be mediated by the inhibition of protein kinase C [105]. Oilier recent studies on the potential vasorelaxant, antioxidant, and cyclic nucleotide phosphodiesterase (PDE) inhibitory effects of the citrus-fruit flavonoids nar-ingenin and hesperetin in intact rat aortic rings have shown that their vasorelaxant effects were mediated by the inhibition of different PDE isoenz5Tnes [106,107]. 

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