Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is dependent on vessel size

Insulin and insulin-like growth factor I (IGF-I) influence numerous metabol ic and mitogenic processes; these hormones also have vasoactive properties. This study examined mechanisms involved in insulin- and IGF-I-induced dila tion in canine conduit and microvascular coronary segments. Tension of coro nary artery segments was measured after constriction with PGF(2 alpha). Int ernal diameter of coronary microvessels (resting diameter = 112.6 +/- 10.1 mu m) was measured after endothelin constriction. Vessels were incubated in control (Krebs) solution and were treated with N-omega-nitro-L-arginine (L -NA), indomethacin, or K+ channel inhibitors. After constriction, cumulativ e doses of insulin or IGF-I (0.1-100 ng/ml) were administered. In conduit a rteries, insulin produced modest maximal relaxation (32 +/- 5%) compared wi th IGF-I (66 +/- 12%). Vasodilation was attenuated by nitric oxide synthase (NOS) and cyclooxygenase inhibition and was blocked with KCl constriction. Coronary microvascular relaxation to insulin and IGF-I was not altered by L-NA, indomethacin, tetraethylammonium chloride, glibenclamide, charybdotox in, and apamin; however, tetrabutylammonium chloride attenuated the respons e. In conclusion, insulin and IGF-I cause vasodilation in canine coronary c onduit arteries and microvessels. In conduit vessels, NOS/cyclooxygenase pa thways are involved in the vasodilation. In microvessels, relaxation to ins ulin and IGF-I is not mediated by NOS/cyclooxygenase pathways but rather th rough K+-dependent mechanisms.