Flow-induced responses in skeletal muscle venules:: modulation by nitric oxide and prostaglandins

Skeletal muscle arterioles dilate in response to increases in flow velocity/wall shear stress (WSS). The effect of flow/WSS an the diameter of skeletal muscle venules and the possible endothelial mediation of the response, however, have not yet been characterized. Thus changes in diameter of pressurized (10 mmHg) and norepinephrine-preconstricted venules (179 +/- 8 mu m in diameter) to increases in perfusate flow before and after endothelium removal or application of inhibitors of NO and prostaglandin (PG) synthesis, NO-nitro-L-arginine (L-NNA, 10(4) M) and indomethacin (Indo, 2.8 x 10(5) M), respectively, were measured. Increases in perfusate flow [elicited by increases in the pressure difference (P-diff) between proximal and distal cannulas] evoked with a delay of 17 +/- 2 s dilations, up to 36 +/- 9 mu m at the highest how a response that was completely eliminated by removal/disruption of the venular endothelium. Calculation of WSS indicated that in endothelium-intact venules, the midpoint of the shear stress-diameter curve was at similar to 8 dyn/cm(2), whereas in endothelium-denuded vessels, shear stress increased in a linear fashion with increases in flow, up to 40 dyn/cm(2). L-NNA significantly reduced flow-induced dilations (from 38 +/- 11 to 17 +/- 9 mu m at 14 mmHg P-diff), whereas in the additional presence of Indo, flow elicited constriction of venules decreasing basal diameter (by 21 +/- 8 mu m at P-diff 12 mmHg). Thus in skeletal muscle venules an increase in sheer stress due to increases in perfusate flow stimulates the release of endothelium-derived NO and PGs eliciting dilation, which in turn, regulates WSS, albeit at a lower value than what is observed in arterioles. In the absence of NO and PGs, flow-induced constriction is revealed, the cause of which remains obscure. From these data, we propose that shear stress-related responses of venules are involved in the regulation of venular resistance, especially during high flow conditions, such as reactive and exercise hyperemia.