Differential mechanisms for insulin-induced relaxations in mouse posterior tibial arteries and main mesenteric arteries.

The characteristics of endothelium-dependent relaxations in response to insulin and acetylcholine (ACh) in the mouse posterior tibial artery (PTA) were studied on wire myograph, and compared to those in the mouse main mesenteric artery (MMA). Insulin-induced relaxation in PTA was reversed by PI3K and Akt inhibitors, LY294002 and triciribine, but not by nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) or guanylate cyclase inhibitor, ODQ. The relaxation in PTA was also inhibited by apamin (small-conductance Ca(2+)-activated K(+) channel blocker) plus charybdotoxin (intermediate-conductance Ca(2+)-activated K(+) channel blocker), elevated KCl or ouabain (Na(+)-K(+) ATPase inhibitor) plus BaCl(2) [inwardly rectifying K(+) (K(IR)) channel inhibitor]; whereas L-NAME but not triciribine inhibited ACh-induced relaxation in PTA. On the other hand, nitric oxide and endothelium-derived hyperpolarizing factor albeit to a less extent mediated both insulin- and ACh-induced relaxations in MMA. The present study is for the first time dissecting out the components of endothelium-dependent relaxation in mouse PTA and suggesting differential responses to different agonists in distinctive blood vessels.