Effects of neutral endopeptidase inhibition on the clearance of exogenously administered endothelin in Sprague-Dawley rats.

The effects of the selective neutral endopeptidase (EC 3.4.24.11, NEP) inhibitor SQ 28,603 on endogenous plasma endothelin (ET) concentration and on the clearance from the circulation of exogenously administered synthetic human ET-1 were examined in Sprague-Dawley rats. Inhibition of NEP by SQ 28,603 (100 μmol/kg intravenously, i.v.) affected neither basal levels of plasma ET nor the cuculatory clearance of an i.v. administered bolus dose (3 nmol/kg) of ET-1. ET-1 produced marked, statistically significant increases in plasma atrial natriuretic peptide (ANP) and cyclic GMP concentrations