FLOW-INDUCED RESPONSES IN SKELETAL-MUSCLE VENULES - MODULATION BY NITRIC-OXIDE AND PROSTAGLANDINS

Skeletal muscle arterioles dilate in response to increases in flow vel ocity/wall shear stress (WSS). The effect of flow/WSS an the diameter of skeletal muscle venules and the possible endothelial mediation of t he response, however, have not yet been characterized. Thus changes in diameter of pressurized (10 mmHg) and norepinephrine-preconstricted v enules (179 +/- 8 mu m in diameter) to increases in perfusate flow bef ore and after endothelium removal or application of inhibitors of NO a nd prostaglandin (PG) synthesis, NO-nitro-L-arginine (L-NNA, 10(4) M) and indomethacin (Indo, 2.8 x 10(5) M), respectively, were measured. I ncreases in perfusate flow [elicited by increases in the pressure diff erence (P-diff) between proximal and distal cannulas] evoked with a de lay 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 v enular endothelium. Calculation of WSS indicated that in endothelium-i ntact 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 ba sal diameter (by 21 +/- 8 mu m at P-diff 12 mmHg). Thus in skeletal mu scle venules an increase in sheer stress due to increases in perfusate flow stimulates the release of endothelium-derived NO and PGs eliciti ng dilation, which in turn, regulates WSS, albeit at a lower value tha n what is observed in arterioles. In the absence of NO and PGs, flow-i nduced constriction is revealed, the cause of which remains obscure. F rom these data, we propose that shear stress-related responses of venu les are involved in the regulation of venular resistance, especially d uring high flow conditions, such as reactive and exercise hyperemia.