EDRF coordinates the behaviour of vascular resistance vessels

Constriction of vascular smooth muscle in response to the stimulus of raised intravascular pressure—the myogenic response1,2— represents a positive feedback mechanism which, if unopposed, could theoretically lead to instability in the intact circulation3,4. Dilation in response to increased intraluminal flow would provide an opposing feedback mechanism which could confer overall stability4. Flow-dependent dilation in conduit vessels5–7 is mediated by endothelium-derived relaxing factor (EDRF)8–14, but the relationship between flow and EDRF activity has not been studied in resistance vessels in situ. We here demonstrate that EDRF can coordinate the aggregate hydrodynamic properties of an intact network. Under control conditions, EDRF maintains a fourth-power relationship between diameter and flow so that the pressure gradient in each vessel asymptotically approaches a constant value at high flow rates. Basal EDRF release may also maintain a similar spatial distribution of flow at different flow rates, even under conditions of moderate pharmacological constriction