Spontaneous contractions of isolated bat wing venules are inhibited by luminal flow

The hypothesis that spontaneous contractions of bat wing venules could be modulated by luminal flow was tested. Single venules (114 +/- 5 microns diam) from the wings of anesthetized pallid bats were dissected, cannulated, and pressurized in vitro. A dual reservoir system was used to independently control luminal pressure and flow. In the absence of flow, and with pressure set to 10 cmH2O, all venules contracted spontaneously at rates between 20 and 40 cycles/min. Pressure elevation over the range of 3-10 cmH2O caused a rapid increase in contraction frequency and decrease in amplitude; pressure reduction caused a rapid decrease in contraction frequency and increase in amplitude. In contrast, initiation of flow resulted in a delayed and gradual reduction of contraction amplitude and/or frequency (sometimes to zero). The net effect of flow was to increase mean diameter and decrease the product of frequency x cross-sectional area. Flow-induced inhibition of venular contraction was eliminated by endothelial denudation but persisted in the presence of NG-monomethyl-L-arginine (10(-4) M) or indomethacin (10(-5) M) in concentrations that blocked the effects of exogenously applied ATP or arachidonic acid, respectively. The flow-induced venular response also persisted in the presence of superoxide dismutase (55 U/ml). Denuded venules responded to flow when placed downstream (i.e., perfused in series) from venules with intact endothelium. These results indicate that luminal flow can modulate the contractile function of bat wing venules via release of a transferable substance from the endothelium. The exact nature of the substance is not yet known but it does not appear to be classical endothelium-derived relaxing factor, a prostaglandin, or an oxygen radical.