CORELEASE OF NITRIC-OXIDE AND PROSTAGLANDINS MEDIATES FLOW-DEPENDENT DILATION OF RAT GRACILIS MUSCLE ARTERIOLES

We have studied the mechanisms responsible for the mediation of flow (shear stress)-induced dilation of isolated arterioles of rat gracilis muscle. Active diameter of arterioles at a constant perfusion pressure (PP, 80 mmHg) was similar to 92 mu m, while their passive diameter (Ca2+-free solution) was similar to 165 mu m. At a constant PP the stepwise increase in flow of the perfusion solution (PS, 0-60 mu l/min in 10-mu l/min steps) elicited a gradual increase in diameter up to similar to 140 mu m. Flow-induced dilations were eliminated by the removal of the endothelium of arterioles (by air). Dilations were significantly reduced by the cyclooxygenase blocker, indomethacin (Indo, 10(-5) M), by the nitric oxide synthase blocker, N-omega-nitro-L-arginine (L-NNA, 10(-4) M), or by the endothelium-derived relaxing factor inhibitor, oxyhemoglobin (Hb, 10(-5) M), as indicated by the signifi cant changes in the slope of the regression lines of the flow-diameter curves. For example, during administration of the inhibitors, dilation to 60 mu l/min perfusate flow was reduced by 41.1, 54.3, and 39.3%, respectively. Combined application of Indo and L-NNA almost completely eliminated flow-induced dilation. Arteriolar dilation maintained calculated wall shear stress close to control values (similar to 30 dyn/cm(2) at 60 mu l/min) despite increases in flow, but when the dilation was inhibited by removal of the endothelium or by the combined administration of Indo and L-NNA, wall shear stress was greatly increased as a function of increases in flow of the PS (similar to 125 dyn/cm(2)). We conclude, that in arterioles of gracilis muscle, in response to increases in shear stress during increased flow conditions, endothelial nitric oxide and prostaglandins are coreleased, evoking dilation, which in a negative feedback manner controls wall shear stress.