Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro

David Hasdai, Robert A. Rizza, David R. Holmes, Darcy M. Richardson, Pinchas Cohen, Amir Lerman

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10-7 mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10-12 to 10-7 mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor N(G)- monomethyl-L-arginine (L-NMMA; 10-4 mol/L) with and without 10-3.5 mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10-2 mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,- α]quinoxalin-1-one (ODQ; 10-5.5 mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28±4% [n=7] and 25±3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl nd TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.

Original languageEnglish (US)
Pages (from-to)228-234
Number of pages7
JournalHypertension
Volume32
Issue number2
DOIs
StatePublished - Aug 1998

Keywords

  • Arteries
  • Endothelium
  • Growth factors
  • Insulin
  • Nitric oxide
  • Pigs
  • Potassium channels

ASJC Scopus subject areas

  • Internal Medicine

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