Increases in intraluminal pressure greatly affect the spontaneous vasomotion of lymphatics and activate the myogenic mechanism intrinsic to the smooth muscle. In addition, endothelial factors are important to maintain adequate lymphatic vasomotion. These findings suggest that intraluminal pressure and endothelial factors can be important contributors to the tone and pumping activity of lymphatics in vivo.

Skeletal muscle arterioles dilate in response to increases in flow velocity/wall shear stress (WSS). The effect of flow/WSS on 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 μm in diameter) to increases in perfusate flow before and after endothelium removal or application of inhibitors of NO and prostaglandin (PG) synthesis, N ω-nitro-l-arginine (l-NNA, 104 M) and indomethacin (Indo, 2.8 × 105 M), respectively, were measured. Increases in perfusate flow [elicited by increases in the pressure difference (Pdiff) between proximal and distal cannulas] evoked with a delay of 17 ± 2 s dilations, up to 36 ± 9 μm at the highest flow, 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 ∼8 dyn/cm2, whereas in endothelium-denuded vessels, shear stress increased in a linear fashion with increases in flow, up to 40 dyn/cm2.l-NNA significantly reduced flow-induced dilations (from 38 ± 11 to 17 ± 9 μm at 14 mmHg Pdiff), whereas in the additional presence of Indo, flow elicited constriction of venules decreasing basal diameter (by 21 ± 8 μm at Pdiff 12 mmHg). Thus in skeletal muscle venules an increase in shear 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.

The pressure-induced myogenic response of large venules of skeletal muscle and its possible interactions with adrenergic receptor activation and endothelial factors have not yet been elucidated. Therefore, first-order venules of rat gracilis muscle were isolated, cannulated, and placed in an organ chamber. Changes in internal diameter of the vessels as a function of perfusion pressure (PP) were obtained. In response to increases in PP (0.5-17.5 mmHg), the diameter of venules increased from 197.1 +/- 23.96 to 369 +/- 14.1 microns. In passive conditions (in Ca(2+)-free solution), the pressure-diameter curve of venules shifted significantly upward. In the presence of norepinephrine (NE; 10(-6) M) in the bath solution, the pressure-diameter curve of active venules shifted significantly downward, and in the pressure-normalized diameter curve, a negative slope developed (-6.1 +/- 4.6). In both the absence and presence of NE, removal of endothelium significantly reduced venular diameters in the pressure ranges of 3-5 and 2-5 mmHg, respectively, but did not change significantly the characteristics of the pressure-diameter curves. These findings indicate that the smooth muscle of venules actively responds to changes in intraluminal pressure. This response is greatly facilitated by NE and modulated by the endothelium. The myogenic response of skeletal muscle venules, especially in the presence of NE, could have a role in the regulation of the resistance and capacitance of venules and, consequently, blood flow and tissue exchange in skeletal muscle.