Endothelin regulates angiotensin-converting enzyme in the mouse kidney.
Using the orally active endothelin-A- (ET(A)) 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 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/l 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/l, 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.
Barton
M
M
Cardiology, University Hospital Zürich and Institute of Physiology, University of Zürich, Switzerland. matthiasbarton@compuserve.com
Carmona
R
R
Krieger
J E
JE
Göettsch
W
W
Morawietz
H
H
d'Uscio
L V
LV
Lattmann
T
T
Lüscher
T F
TF
Shaw
S
S
D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000201:enzymology*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004041:Dietary Fats; D019332:Endothelin-1; D008055:Lipids; D009566:Nitrates; D009573:Nitrites; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D007703:Peptidyl-Dipeptidase A