Using the orally active endothelin-A- (ETA) receptor antagonist LU135252 we
determined whether endothelin-1 (ET-1) and/or dietary fat may be involved
in angiotensin-converting enzyme (ACE) regulation in vivo. In C57BL6/J mice
, renal and pulmonary tissue ACE activity (nmol/l His-Leu/mg protein) was m
easured and ACE mRNA expression, tissue ET-1 protein content and nitrite/ni
trate level were measured in the kidney. Western-type diet increased renal
ACE activity by 70% (55 +/- 4 vs 33 +/- 3 nmol/l His-Leu/mg protein, p < 0.
05) and increased renal ET-1 levels (267 +/- 19 pg/g vs 190 +/- 18, p < 0.0
5). Chronic LU135252 treatment completely prevented activation of renal ACE
activity (13.3 +/- 0.3 His-Leu/mg protein nmol/l, p < 0.05) independent of
ACE mRNA expression or renal ET-1 protein levels. Thus, dietary fat activa
tes renal ACE activity and ET-1 is involved in regulation of tissue ACE act
ivity in vivo independently of ACE mRNA expression.