Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c

David Hasdai, David R. Holmes, Darcy M. Richardson, Uzzi Izhar, Amir Lerman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Objective: To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. Background: Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. Methods: Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10-10 - 10-6 M) or of sarafotoxin-6c (ETB-receptor agonist; 10-11 - 10-7 M). In additional experiments, endothelin-1 or sarafotoxin- 6c were added after incubation with 10-~ M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. Results: The maximal contractions to endothelin-1 in vessels with and without endothelium were 158±8 and 200±21%, respectively (p<0.05 at 10-8.5 - 10-6.5 M). Both insulin (at 10-7 - 10-6 M) and IGF-I (at 10-6.5 - 10-6 M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10-7 and 10-6 M for insulin and 10-7.5 - 10-6 M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54±13 and 84±7%, respectively (p<0.05 at 10-9 10-8.5 and 10-7 M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. Conclusion: Insulin and IGF-I attenuated ETA-receptor- mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.

Original languageEnglish (US)
Pages (from-to)644-650
Number of pages7
JournalCardiovascular research
Volume39
Issue number3
DOIs
StatePublished - Sep 1 1998

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Keywords

  • Coronary artery
  • Endothelin
  • Endothelin-I
  • Insulin
  • Insulin-like growth factor I
  • Pig
  • Sarafotoxin- 6c

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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