Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival

Chikako Takahashi, Yutaka Kagaya, Shigeto Namiuchi, Morihiko Takeda, Mitsumasa Fukuchi, Hiroki Otani, Mototsugu Ninomiya, Yuriko Yamane, Masahiro Kohzuki, Jun Watanabe, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.

Original languageEnglish
Pages (from-to)29-38
Number of pages10
JournalJournal of cardiovascular pharmacology
Volume38
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Endothelin
  • Endothelin receptor antagonist
  • Left ventricular remodeling
  • Myocardial infarction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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