EDRF and the regulation of vascular tone

Vascular endothelium is now known to produce a vasodilator agent, known as endothelium derived relaxing factor (EDRF) and recently shown to be nitric oxide. It acts locally on subjacent vascular smooth muscle by stimulating soluble guanylate cyclase to increase cyclic GMP levels and so reduce cytosolic free calcium. EDRF activity varies widely between different artery types and can be stimulated by various pharmacological agents and by flow. Studies in the intact vascular bed of the buffer-perfused rabbit ear show that EDRF activity is high in resistance vessels (particularly those of ca. 150 microns diameter), that EDRF is responsible for a 4th power relationship of diameter to flow in response to acute changes in flow (so limiting pressure gradients needed to increase flow rate), and that basal EDRF activity maintains geometric similarity of vessel diameters (implying that the spatial distribution of flow remains constant at different flow rates).