Insulin and IGF-1 induced vasodilation in canine coronary microvessels

Insulin and insulin-like growth factor 1 (IGF-1) are structurally related peptides capable of stimulating a variety of metabolic and mitogenic processes. Insulin has been demonstrated to cause dilatation in a variety of vascular tissues. The purpose of this study was to determine mechanisms involved in coronary microvascular dilation to insulin and IGF-1. Epicardial coronary arterioles (diameter = 101.8 ± 9.2 μm) from 24 mongrel dogs (5-8 kg) were mounted onto pipettes in warmed (37° C), oxygenated (20% O₂, 75% N₂ and 5% CO₂) Kreb's buffer (distending pressure 20 mmHg, no flow). Vessels were incubated in control solution, L-NNA (10 μM), glibenclamide (1 μM), indomethacin (10 μM), or tetraethylammonium chloride (TEA, 1 mM) for 30 minutes. After constriction with endothelin (30-50% of resting diameter) cumulative doses of insulin and IGF-1 (0.1 - 100 ng/ml), were added extraluminally to the bath and internal diameters measured by video microscopy. Results: Insulin and IGF-1 produced similar relaxation in coronary arterioles (Max. relaxation 83.5 ± 19.1 and 63.64 ± 13.45 respectively). L-NNA, glibenclamide, indomethacin or TEA did not alter the response to insulin or IGF-1. We conclude that in canine coronary microvessels, relaxation to insulin and IGF-1 is similar and not mediated by nitric oxide, prostacyclin, or select K⁺ channels.