Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation

Biochem Biophys Res Commun. 1997 Sep 29;238(3):861-5. doi: 10.1006/bbrc.1997.7394.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Aorta / physiology
  • Aspartic Acid Endopeptidases / blood*
  • Aspartic Acid Endopeptidases / physiology
  • Blood Pressure / drug effects
  • Endothelin Receptor Antagonists
  • Endothelin-1 / blood*
  • Endothelin-1 / drug effects
  • Endothelin-1 / metabolism
  • Endothelin-Converting Enzymes
  • Femoral Artery / drug effects
  • Femoral Artery / enzymology
  • Femoral Artery / physiology
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Kidney / drug effects
  • Kidney / enzymology*
  • Male
  • Metalloendopeptidases
  • Muscle Contraction / drug effects
  • Phenylpropionates / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Inbred WKY
  • Receptor, Endothelin A
  • Receptors, Endothelin / physiology*

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Iodine Radioisotopes
  • Phenylpropionates
  • Pyrimidines
  • Receptor, Endothelin A
  • Receptors, Endothelin
  • Angiotensin II
  • darusentan
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes