Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation.
Angiotensin II (Ang II)-stimulated expression of endothelin-1 (ET-1) mRNA is blocked by ETA antagonists in vitro. We studied effects of Ang II (200 ng/kg/min) and ETA antagonist LU135252 (50 mg/kg/d) in WKY rats in vivo investigating vascular and renal ET-1 protein expression, functional endothelin converting enzyme (ECE) activity, and clearance of (125I)ET-1. Infusion of Ang II for two weeks increased ET-1 protein content in aorta (4.7-fold) and femoral artery (1.6-fold) with and without endothelium and in kidneys (3-fold, p<0.05) and enhanced functional ECE activity (p<0.05). The Ang II-induced increase in tissue ET-1 content and functional ECE activity was completely prevented by LU135252 (p<0.05). Chronic treatment of control animals with LU135252 lowered basal vascular but not renal ET-1 content (p<0.05 vs. control). Clearance of 125IET-1 was unaffected by the treatments. It is concluded that Ang II increases ET-1 protein and functional ECE activity in vascular smooth muscle and kidney through ETA-receptors in vivo.
Barton
M
M
Cardiology, University Hospital Zürich, Institute of Physiology, Switzerland.
Shaw
S
S
d'Uscio
L V
LV
Moreau
P
P
Lüscher
T F
TF
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000097:blood* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D005263:Femoral Artery / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008666:Metalloendopeptidases; D009119:Muscle Contraction / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007457:Iodine Radioisotopes; D010666:Phenylpropionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D000804:Angiotensin II; C107831:darusentan; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes