Involvement of NO and EDHF in flow-induced vasodilation in isolated hamster cremasteric arterioles

Flow-induced vasodilation in hamster cremasteric arterioles was investigated with special reference to the roles of nitric oxide ( NO) and endothelium-derived hyperpolarizing factor ( EDHF). Arterioles (similar to 60 mu m resting diameter) were cannulated, and suffused with MOPS solution at 37 degrees C ( mean intraluminal pressure: 80 cm H2O). Step increases in the perfusate flow elicited a dose-dependent vasodilation, which was almost proportional to the increases in calculated wall shear stress (WSS). N-omega-nitro L-arginine methyl ester (L-NAME, 100 mu M) reduced the flow- induced vasodilation by F50%, whereas indomethacin (10 mu M) produced no significant effect. In the presence of L- NAME, the residual vasodilation was eliminated by treatment with the cytochrome P-450 monooxygenase inhibitor 17-octadecynoic acid (17-ODYA, 50 mu M), sulfaphenazol ( 10 mu M), tetraethylammonium ( TEA, 3 mM; a nonselective Ca2+- activated K+ channel inhibitor), or charybdotoxin (ChTX, 0.1 mu M; intermediate or large conductance Ca2+- activated K+ channel inhibitor). In the absence of L- NAME, the dilation was also reduced by F50% by treatment with 17-ODYA, TEA, or ChTX. The residual vasodilation was eliminated by additional treatment with L-NAME. The inhibitor of ATP-sensitive K+ channels (K-ATP), glibenclamide, also caused a significant, but partial, reduction of the flow-induced vasodilation. The residual vasodilation was completely reduced by additional treatment with 17-ODYA, but not L-NAME. These findings suggest that in hamster cremaster, higher flow rate produces NO, K-ATP, and EDHF vasodilation of the arterioles under physiological conditions. Copyright (C) 2005 S. Karger AG, Basel.