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/1 His-Leu/mg protein) was measured and ACE mRNA expression, tissue ET-1 protein content and nitrite/nitrate level were measured in the kidney. Western-type diet increased renal ACE activity by 70% (55 ± 4 vs 33 ± 3 nmol/1 His-Leu/mg protein, p < 0.05) and increased renal ET-1 levels (267 ± 19 pg/g vs 190 ± 18, p < 0.05). Chronic LU135252 treatment completely prevented activation of renal ACE activity (13.3 ± 0.3 His-Leu/mg protein nmol/1, p < 0.05) independent of ACE mRNA expression or renal ET-1 protein levels. Thus, dietary fat activates renal ACE activity and ET-1 is involved in regulation of tissue ACE activity in vivo independently of ACE mRNA expression.
*†Cardiology, University Hospital Zürich and Cardiovascular Research Laboratory, Institute of Physiology, University of Zürich, Switzerland, †Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paolo School of Medicine, São Paulo, Brazil, ‡Institute of Pathophysiology, Faculty of Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany, and §Department of Clinical Research, University of Bern, Switzerland
Address correspondence and reprint requests to Matthias Barton, Division of Cardiology, Department of Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail: [email protected]
Presented in part at the Gordon Research Conference on Angiotensin, August 8-13, 1999, Queen's College, Oxford, U.K
© 2000 Lippincott Williams & Wilkins, Inc.