Endothelin gene expression during ischemia and reperfusion

Katalin Keltai, Hajnalka Vágó, András Zsáry, István Karádi, Violetta Kékesi, Alexander Juhász-Nagy, Béla Merkely

Research output: Article

5 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) probably plays an important role in myocardial damage in acute ischemia. Coronary sinus ET-1 and its precursor big endothelin-1 (big ET-1) levels and also tissue levels of preproendothelin-1 mRNA (ET-1 mRNA) were investigated in an in vivo canine ischemia-reperfusion model in nine consecutive mongrel dogs, surviving 30-minute ligation of the left descending coronary artery followed by a 90-minute reperfusion period. Samples were collected before and at the end of ischemia and during reperfusion. ET-1 and big ET-1 were obtained by immunoprecipitation and detected by western blotting. The ET-1 mRNA level was assessed by reverse transcription-polymerase chain reaction. During ischemia the plasma ET-1 levels and big ET-1 levels did not change significantly, while the myocardial ET-1 mRNA level decreased to 57.8%. During reperfusion an increase of the coronary sinus ET-1 and big ET-1 levels was observed (control versus reperfusion, 90 minutes; ET-1, 15.2 ± 4.18 fmol/mL versus 23.2 ± 5.23 fmol/mL, P < 0.01 ; big ET-1, 14.7 ± 5.9 fmol/mL versus 27.2 ± 7.1 fmol/mL, P < 0.001). Simultaneously, the ET-1 mRNA level increased by 322% relative to the ischemic and by 214% relative to the baseline level. The decrease of ET-1 mRNA during ischemia may be due to degradation and decreased metabolism in the hypoxic cells locally. The elevation of the ET-1 mRNA level during reperfusion indicates rapid big ET-1 synthesis. This was confirmed by the increases in big ET-1 and ET-1 plasma levels. This latter can be associated with the generation of reperfusion arrhythmias or other complications of acute myocardial infarction.

Original languageEnglish
Pages (from-to)S198-S201
JournalJournal of cardiovascular pharmacology
Volume44
Issue numberSUPPL. 1
DOIs
Publication statusPublished - nov. 1 2004

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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