Effect of neutral endopeptidase on plasma and tissue concentrations of vaso-active intestinal peptide

1. This study sought to determine if neutral endopeptidase metabolizes vaso-active intestinal peptide (VIP) and whether changes in the activity of this enzyme might explain the change in VIP metabolism which follows gastric sodium loading. The study also investigated whether prolonged inhibition of neutral endopeptidase was associated with inhibition of further secretion of VIP. 2. Male Sprague-Dawley rats were given the neutral endopeptidase inhibitor UK77,568 (10 mg/kg), or vehicle, tail vein injected, once or daily for 4 days. Two hours after injection the rats were anaesthetized, blood sampled to determine plasma concentrations of VIP and the hearts were harvested. Plasma and tissue concentrations of VIP were determined by radio-immunoassay. 3. Plasma VIP increased in response to UK77,568 at day 1 (P < 0.0005) but did not differ from control at day 4. The concentration of VIP in the heart did not increase at day 1 but had increased significantly at day 4 (P < 0.01). 4. It was concluded that neutral endopeptidase may metabolize VIP. Further, the increased concentration of VIP in the heart and the return of its plasma concentration to control levels at day 4 may be consistent with suppression of continued VIP secretion.