Modulation of nitric oxide metabolism

Nitric oxide is synthesized by a family of nitric oxide synthases, of which there are three well-characterized isoforms, products of three distinct genes and initially named after the tissues from which they were first isolated the constitutively expressed neuronal 

Recently, the biological impact of dietary polyphenols has been associated with the endothelial metabolism of NO. In particular, it has been shown that mono-O-methylated flavanols and other flavonoids by inhibition of endothelial NADPH oxidase suppress the formation of superoxide radical, that otherwise eliminates NO via diffusion-controlled formation of peroxynitrite (Steffen et al, 2008). Such a mechanism, preserving or enhancing the bioavailability of NO, may underlie the improvement of vascular endothelial function by certain flavonoid structures and its metabolites via, for instance, dilation of arterial vessels and lowering of blood pressure (Steffen et al, 2008). 

Another line of investigation is bridging polyphenol activity with NO bioavailability via the chemical reduction of nitrite to NO (Takahama et al, 2002 Peri et al, 2005 Gago et al, 2007). The redox properties that have been proposed to confer polyphenols with antioxidant activity by quenching oxidizing radicals may, alternately, endow the phenolic compounds with the capacity to promote the formation of NO from nitrite, particularly in the gastrointestinal tract, a location where both nitrite and polyphenols achieve high concentrations. 

In fact, soon after NO identification in a biological setting it was realized that, independently of nitric oxide synthase, NO could be formed from nitrite (Zweier et al, 1995) by heme proteins, xanthine oxidoreductase, and thiol-containing enzymes during 

Biological effects (heme, RSNO) - local or systemic  

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Numerous flavonoids have been reported to affect cellular signaling processes, from kinases to transcription factors. In fact, oligomeric procyanidins from pine bark were found to prevent the activation of the proinflammatory transcription factor NF-k-B on ultraviolet (UV) exposure [3]. The same procyanidins are also potent modulators of nitric oxide metabolism [4,5]. 

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