Mechanisms for nitrite loss from the stomach.

Area of Science:

• Gastroenterology
• Pharmacokinetics
• Biochemistry

Background:

• Nitrite is a crucial molecule in various physiological processes.
• Understanding nitrite's fate in the stomach is vital for its therapeutic and toxicological implications.
• Previous studies have not fully elucidated the mechanisms of gastric nitrite loss.

Purpose of the Study:

• To investigate the quantitative aspects of nitrite loss from the stomach.
• To determine the primary mechanisms responsible for nitrite disappearance in the gastric lumen.
• To model the factors influencing gastric nitrite concentrations.

Main Methods:

• In vivo study using dogs with Thomas cannulas for direct gastric access.
• Infusion of sodium nitrite with polyethylene glycol (PEG) as a volume marker.
• Serial sampling to measure total nitrite concentration, PEG dilution, and stomach volume changes.
• In vitro kinetic studies to assess chemical reaction rates.
• Mathematical modeling to simulate gastric nitrite dynamics.

Main Results:

• Nitrite loss was rapid, with concentrations halving within 10 minutes.
• Gastric absorption was the predominant loss mechanism, followed by dilution and chemical reactions.
• Nitrite absorption followed first-order kinetics, with a permeability-area product (PA) of approximately 0.6 L/h.
• Increased luminal pH (from 2 to 7) reduced apparent PA by three-fold.
• Stimulated gastric acid secretion (pentagastrin) halved nitrite absorption compared to inhibited secretion (cimetidine) or no drug, independent of pH.

Conclusions:

• Nitrite is readily absorbed from the stomach, likely as undissociated nitrous acid (HNO2).
• Gastric pH significantly influences nitrite absorption.
• Active gastric acid secretion appears to inhibit nitrite absorption, suggesting a complex regulatory mechanism.
• A mathematical model was developed to describe nitrite behavior in the stomach.