Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.

Dietary NO (nitrate) and NO (nitrite) support ˙NO (nitric oxide) generation and downstream vascular signaling responses. These nitrogen oxides also generate secondary nitrosating and nitrating species that react with low molecular weight thiols, heme centers, proteins, and unsaturated fatty acids. To explore the kinetics of NOand NOmetabolism and the impact of dietary lipid on nitrogen oxide metabolism and cardiovascular responses, the stable isotopes NaNO and NaNO were orally administered in the presence or absence of conjugated linoleic acid (cLA). The reduction of NO to NO was indicated by electron paramagnetic resonance spectroscopy detection of hyperfine splitting patterns reflecting NO-deoxyhemoglobin complexes. This formation of NO also translated to decreased systolic and mean arterial blood pressures and inhibition of platelet function. Upon concurrent administration of cLA, there was a significant increase in plasma cLA nitration products 9- and 12-NO-cLA. Coadministration of cLA with NO also impacted the pharmacokinetics and physiological effects of NO, with cLA administration suppressing plasma NOand NOlevels, decreasing NO-deoxyhemoglobin formation, NOinhibition of platelet activation, and the vasodilatory actions of NO, while enhancing the formation of 9- and 12-NO-cLA. These results indicate that the biochemical reactions and physiological responses to oral NOand NOare significantly impacted by dietary constituents, such as unsaturated lipids. This can explain the variable responses to NOand NOsupplementation in clinical trials and reveals dietary strategies for promoting the generation of pleiotropic nitrogen oxide-derived lipid signaling mediators. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01681836.