Tissue neutral endopeptddase activity in hamsters with spontaneous hypertension

The purpose of this study was to determine tissue neutral endopeptidase (EC 3.4.24.11) activity in adult male hamsters with spontaneous hypertension (n=8) and in age/genetically-matched normotensive controls (n=9). Mean systemic arterial blood pressure was 163±11 mmHg and 99±3 mmHg in hamsters with and without hypertension, respectively (p<0.05; mean±SEM). Neutral endopeptidase activity in tissue homogenatcs was determined spcctrophotometrically using the substrate 3-carboxypropranoylalanyl-alanyl-leucine-4 nitroanilide supplemented with bacterial (Streptomyccs griseus) aminopeptidasc I. We found that neutral endopeptidase activity was significantly higher in the kidney and cheek pouch and significantly lower in the heart and aorta of hypertensive hamsters in comparison to normotensive controls (p<0.05). Phosphoramidon and thiorphan inhibited cheek pouch neutral endopeptidase activity in a concentration-dependent fashion and to a similar extent in both groups with an IC₅₀ of 3 nM and 13 nM, respectively. Captopril, an inhibitor of angiotensin I-converting enzyme, had no significant effects on cheek pouch neutral endopeptidase activity in both groups. Cheek pouch neutral endopeptidase activity increased as chloride anion concentration in the assay buffer was increased. Substituting citrate for chloride anion in the assay buffer abrogated cheek pouch neutral endopeptidase activity. We conclude that tissue neutral endopeptidase activity differs in hamsters with and without hypertension.