Arteriolar dilation produced by venule endothelium-derived nitric oxide

Objective: We conducted bioassay experiments to determine whether nitric oxide produced by endothelial cells (endothelial-derived nitric oxide, or EDNO) within large venules could act to dilate arterioles. Methods: Ln these experiments, parallel segments of first-order arterioles and venules mere isolated from skeletal muscle and mere cannulated in series with a lass connecting tube (length: 300-500 mu m). Arterioles were mechanically denuded of endothelium by a delicate yet abrasive rubbing technique. Venular endothelium remained intact. Endothelial denudation of arterioles was confirmed by the absence of dilation during exposure to acetylcholine (10(-6) mol/L). The cannulated vessels were pressurized to 30 cm H2O and the arterioles pre constricted by approximately 50% with norepinephrine (10(-10) mol/L). Results: Topical applications of acetylcholine (10(-6) mol/L) or bradykinin (10(-9) mol/L) during luminal per fusion from venule to arteriole produced significant arteriolar dilation. In contrast, a slight arteriolar constriction was observed when the direction of flow was reversed (i.e., arteriole to venule) in the presence of either acetylcholine (10(-6) mol/L) or bradykinin (10(-9) mol/L). Inhibition of venular EDNO with N-G-monomethyl-L-arginine (L-NMMA; 10(-5) mol/L; 1 hour) completely abolished the arteriolar dilation observed in response to acetylcholine or bradykinin during venule to arteriole perfusion. Conclusions: These results demonstrate that venular-derived EDNO can relax arteriolar vascular smooth muscle.