Reciprocal regulation of angiotensin converting enzyme and neutral endopeptidase in rats with experimental hypertension.

Abstract

Angiotensin I is a substrate for both the angiotensin converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP). The present study examined the hypothesis that a high ACE expression is associated with a low NEP activity. Male Sprague-Dawley rats had two-kidney, one-clip (2K1C), N(G)-nitro-L-arginine methyl ester (L-NAME) or deoxycorticosterone acetate (DOCA)-salt hypertension, which were either angiotensin-dependent or -independent. The expression of ACE and NEP mRNA was determined in the thoracic aorta by a reverse transcription-polymerase chain reaction. The catalytic activity of NEP was measured by fluorometry. The expression of ACE was increased in 2K1C and L-NAME hypertension, and decreased in DOCA-salt hypertension. Conversely, the expression of NEP was decreased in 2K1C and L-NAME hypertension, and increased in DOCA-salt hypertension. The catalytic activity of NEP was altered similarly as its expression. These results suggest that ACE expression is inversely related to vascular NEP activity in certain forms of hypertension.