The enhancement of preproendothelin-1 synthesis and the acceleration of endothelin-1 processing in the acute hypoxic rat aorta

J Cardiovasc Pharmacol. 2004 Nov:44 Suppl 1:S207-10. doi: 10.1097/01.fjc.0000166235.18959.2a.

Abstract

Wistar rats were deeply anesthetized and perfused by Hanks' solution bubbled with either 95% air and 5% CO2 (normoxic group) or 95% N2 and 5% CO2 (hypoxic group) from the thoracic aorta for 30 minutes. The isolated abdominal aortas were used for electron microscopy, immunocytochemistry of endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1), and in situ hybridization of preproendothelin-1 mRNA. A remarkable increase in the number of Weibel-Palade bodies, storage sites of ET-1 and ECE-1, occurred in the hypoxic group when compared with the normoxic group. Immunoreactivities for ET-1 and ECE-1, and signals for preproendothelin-1 mRNA were seen along the endothelia of both groups, but the intensities were significantly elevated in the hypoxic group. The increase in the number of ECE-1 immunoreactive gold particles was noticed in Weibel-Palade bodies in the hypoxic group. These findings indicate the enhancement of preproendothelin-1 synthesis in the rat aortic endothelial cells and the acceleration of ET-1 processing in Weibel-Palade bodies of such cells in an acute hypoxic condition.

MeSH terms

  • Acute Disease
  • Animals
  • Aorta, Abdominal / enzymology
  • Aorta, Abdominal / metabolism*
  • Aorta, Abdominal / ultrastructure
  • Aspartic Acid Endopeptidases / metabolism
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Endothelin-Converting Enzymes
  • Hypoxia / enzymology
  • Hypoxia / metabolism*
  • Hypoxia / pathology
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Metalloendopeptidases / metabolism
  • Microscopy, Immunoelectron
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Up-Regulation
  • Weibel-Palade Bodies / enzymology
  • Weibel-Palade Bodies / metabolism*
  • Weibel-Palade Bodies / ultrastructure

Substances

  • Endothelin-1
  • Protein Precursors
  • RNA, Messenger
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes