© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c
Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA
* Corresponding author. Tel.: +1-507-255-4152; Fax: +1-507-255-2550; E-mail: lerman.amir@mayo.edu
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 10–8 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.
KEYWORDS Pig; Insulin; Insulin-like growth factor I; Endothelin-1; Sarafotoxin-6c; Endothelin receptors; Coronary artery
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