Insulin-Induced Arteriolar Dilation after Tyrosine Kinase and Nitric Oxide Synthase Inhibition in Hamster Cheek Pouch Microcirculation

Abstract

We investigated the effects of tyrosine kinase (TK) and nitric oxide synthase (NOS) inhibition on insulin-induced dilation of arterioles. We determined the arteriolar diameter, red blood cell velocity (V_RBC) and blood flow changes in hamster cheek pouch microcirculation as affected by insulin in presence of TK and NOS inhibitors, genistein, piceatannol and N^G-monomethyl-L-arginine (L-NMMA). Microvessels were visualized by a fluorescent microscopy technique. Arteriolar diameter and V_RBC were measured after topical application of insulin and genistein or piceatannol or L-NMMA. Insulin (10 µU/ml) induced diameter and V_RBC increase in A3 and A2 arterioles by 30 ± 5 and 123 ± 4%, 16 ± 4 and 102 ± 3%, as percent of baseline values, respectively. After genistein or piceatannol prior to insulin A3 and A2 arterioles dilated by 10 ± 4, 5 ± 2% and 9 ± 4, 2 ± 1%, respectively. After L-NMMA prior to insulin A2 and A3, arteriole diameters increased by 12 ± 3 and 7 ± 2%, respectively. V_RBC increased significantly in all the cases. TK and NOS inhibitors applied together abolished insulin-induced dilation with a reduction in V_RBC and blood flow. In conclusion, full insulin-induced dilation of hamster cheek pouch arterioles requires TK signaling pathways. Furthermore, activation of insulin receptors, as well as other TK receptors, appears to be required for vasomotor tone regulation.