Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation

Nitrite, considered a biological waste and toxic product, is being regarded as an important physiological molecule in nitric oxide (NO) biochemistry. Because the interaction of dietary phenolic compounds and nitrite would be kinetically (due to the high concentrations achieved) and thermodynamically (on basis of the redox potentials) feasible in the stomach, we have studied the potential reduction of nitrite by polyphenols present in several dietary sources. By measuring the time courses of *NO production in simulated gastric juice (pH 2), the efficiency of the compounds studied is as follows: Epicatechin-3-O-gallate>quercetin>procyanidin B8 dimer>oleuropein>procyanidin B2 dimer>chlorogenic acid>epicatechin>catechin>procyanidin B5 dimer. The initial rates of *NO production fall in a narrow range (ca. 1-5 microMs(-1)) but the distinct kinetics of the decay of *NO signals suggest that competition reactions for *NO are operative. The proof of concept that, in the presence of nitrite, phenol-containing dietary products induce a strong increase of *NO in the stomach was established in an in vivo experiment with healthy volunteers consuming lettuce, onions, apples, wine, tea, berries and cherries. Moreover, selected mixtures of oleuropein and catechin with low nitrite (1 microM) were shown to induce muscle relaxation of stomach strips in a structure-dependent way. Data presented here brings strong support to the concept that polyphenols consumed in a variety of dietary products, under gastric conditions, reduce nitrite to *NO that, in turn, may exert a biological impact as a local relaxant.