Organ uptake and release of inorganic nitrate and nitrite in the pig.

Numerous studies have shown beneficial cardiovascular and metabolic effects of dietary nitrate but the release or uptake of these anions on an organ level is still poorly elucidated. Here we administered sodium nitrate in the pig and measured acute changes in release/uptake of nitrate and nitrite across several organs as well as cardiovascular and metabolic functions. In 17 anesthetized pigs multiple venous catheters and arterial ultrasonic blood flow probes were positioned. After pretreatment with the NO synthase (NOS) inhibitor l-NAME to minimize involvement of NOS-dependent nitrate/nitrite generation, the animals received bolus injections of either sodium nitrate or sodium chloride. Organ blood flows and release/uptake of nitrate and nitrite were measured in the pulmonary, splanchnic, hepatic and renal circulations for up to two hours. In addition, small intestinal luminal NO, gut secretion of nitrate, as well as hepatic and renal NADPH oxidase activity were measured. At baseline there was a significant uptake of nitrite in the liver and kidneys together with a release of nitrite from the lungs. In the control pigs, arterial plasma nitrite progressively declined during the observation period (-54%) but was stable in the nitrate group, indicating conversion of nitrate to nitrite. Sodium nitrate led to a marked accumulation of nitrate in the small intestinal lumen with a parallel increase in luminal nitrite. This was coupled with release of nitrite in the portal vein and a concomitant uptake of this anion in the liver. There was a trend towards reduced NADPH oxidase-dependent superoxide generation in the liver but an increase in the kidney. Nitrate had no acute effects on cardiovascular parameters or regional and systemic oxygen consumption. In conclusion, we found a notable difference in release and uptake of nitrate and nitrite between the organs investigated. Our findings indicate an acute conversion of nitrate to nitrite, most likely independent of oral bacteria but by a mammalian nitrate reductase and/or gut bacteria.

Duke Scholars

Author Ting Yang Medicine, Nephrology