Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / pharmacology*
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Animals
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Aorta / drug effects
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Aorta / enzymology
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Aorta / physiology
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Aspartic Acid Endopeptidases / blood*
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Aspartic Acid Endopeptidases / physiology
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Blood Pressure / drug effects
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Endothelin Receptor Antagonists
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Endothelin-1 / blood*
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Endothelin-1 / drug effects
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Endothelin-1 / metabolism
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Endothelin-Converting Enzymes
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Femoral Artery / drug effects
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Femoral Artery / enzymology
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Femoral Artery / physiology
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In Vitro Techniques
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Iodine Radioisotopes
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Kidney / drug effects
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Kidney / enzymology*
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Male
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Metalloendopeptidases
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Muscle Contraction / drug effects
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Phenylpropionates / pharmacology
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Pyrimidines / pharmacology
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Rats
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Rats, Inbred WKY
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Receptor, Endothelin A
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Receptors, Endothelin / physiology*
Substances
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Endothelin Receptor Antagonists
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Endothelin-1
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Iodine Radioisotopes
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Phenylpropionates
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Pyrimidines
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Receptor, Endothelin A
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Receptors, Endothelin
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Angiotensin II
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darusentan
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Aspartic Acid Endopeptidases
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Metalloendopeptidases
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Endothelin-Converting Enzymes