Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro.
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,-alpha]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.
Hasdai
D
D
Division of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
Rizza
R A
RA
Holmes
D R
DR
Richardson
D M
DM
Cohen
P
P
Lerman
A
A
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase