Metabolism of atrial natriuretic peptide. Extraction by organs in the rat

The pharmacokinetics and metabolism of atrial natriuretic peptide (ANP24) were investigated in male Sprague-Dawley rats. Animals were instrumented with arterial and venous catheters to infuse ANP24 and sample blood at various systemic locations; ANPir concentrations were determined by radioimmunoassay. Total clearances (TC) were 150 +/- 15 and 90 +/- 3 ml of blood/min/kg at infusion rates of 137 and 833 ng/min/kg and the half-life of ANPir was 35 +/- 5 seconds. The volume of distribution was 87 +/- 8 ml/kg at the high infusion rate. The kidneys' extraction ratios (E) of ANPir at the two rates of infusion were 0.55 and 0.61, respectively, whereas the intestines' were 0.44 and 0.27. E values of the muscle/sex organs were 0.43 and 0.54 at the two infusion rates. In contrast, no significant degree of extraction was observed for the liver or the heart and lungs. Taking regional blood flow into account, the kidneys were responsible for one sixth to one third of TC while the intestines accounted for one sixth of TC. We conclude that ANP24 is cleared from the blood at a relatively high rate under steady state conditions and that the kidneys, intestines, and muscle/sex organs contribute to its metabolic fate.