Oral sodium regulates extrahepatic metabolism of vasoactive intestinal peptide

1. Gastric sodium loading causes release of vasoactive intestinal peptide from the gastrointestinal tract and, in rabbits on a low-sodium diet, an apparent decrease in metabolism of vasoactive intestinal peptide by the liver. Other workers have shown that decreased hepatic metabolism of vasoactive intestinal peptide is accompanied by an increase in pulmonary metabolism of vasoactive intestinal peptide. To determine whether oral sodium loading also regulates non-hepatic metabolism of vasoactive intestinal peptide, metabolic clearance studies of intravenously infused vasoactive intestinal peptide were performed. These studies were performed in male New Zealand White rabbits equilibrated on normal- and low-sodium diets before and after an acute gastric sodium load of 1.5 mmol/kg. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly greater in rabbits on the low-sodium diet than in rabbits on the normal-sodium diet both before (P less than 0.025) and after (P less than 0.05) a gastric sodium load. Significant decreases in metabolic clearance rate were observed in response to the sodium load in both dietary groups (normal-sodium diet, P less than 0.05; low-sodium diet, P less than 0.025). The theoretical secretion rate of vasoactive intestinal peptide also fell after the gastric sodium load in rabbits on the low-sodium diet (P less than 0.05) and the half-life of vasoactive intestinal peptide increased (P less than 0.01). 3. We conclude that the non-hepatic metabolism of vasoactive intestinal peptide appears to be responsive to both chronic dietary sodium intake and acute gastric sodium loading.