[Role of endothelium-derived hyperpolarizing factor in insulin-induced vasodilation in rat mesenteric artery]

Endothelium-derived hyperpolarizing factor (EDHF) as a factor in blood pressure regulation has received attention recently. However, its role in insulin-induced vasodilation is not clear. We investigated the mechanism of vasodilation induced by insulin in vitro using mesenteric arteries isolated from normotensive rats. The 2nd branch of the mesenteric artery was isolated from male Sprague-Dawley rats (12-14 weeks old), mounted on microcannules in a chamber and perfused with Krebs solution. The diameter of this segment was measured continuously with a video system under the following conditions: intraluminal insulin administration (10 and 100 mU/ml) with and without pretreatment by denudation, N omega-methyl-L-arginine methyl ester (L-NAME), indomethacin, tetrabuthylammonium (TBA, non-specific Ca2+ activated K channel blocker), charybdotoxin (ChTx, large-conductance Ca2+ activated K channel blocker), apaminn (small-conductance Ca2+ activated K channel blocker) or Na+/k(+)-ATPase blocker (ouabain). Insulin treatment induced dose-dependent vasodilation. The effects of insulin were significantly suppressed by denudation, TBA, apamin, and ChTx. L-NAME, indomethacin and ouabain did not influence the insulin-induced vasodilation. Results suggested that insulin dilates small arteries by activating the Ca2+ activated K channel.