From the Divisions of Internal Medicine and Cardiovascular Diseases
(D.H., D.R.H., D.M.R., A.L.), and Endocrinology and the Endocrine Research
Unit (R.A.R.), Mayo Clinic and Foundation, Rochester, Minn; and the Division
of Endocrinology and Department of Pediatrics, University of Pennsylvania,
Philadelphia, Pa (P.C.).
Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu
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
NG-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,-
© 1998 American Heart Association, Inc.
Scientific Contributions
Insulin and Insulin-like Growth Factor-I Cause Coronary Vasorelaxation In Vitro
]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 and
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.
Key Words: insulin • growth factors • pigs • arteries • endothelium • potassium channels • nitric oxide
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