ARTERIOLAR DILATION PRODUCED BY VENULE ENDOTHELIUM-DERIVED NITRIC-OXIDE

Objective: We conducted bioassay experiments to determine whether nitr ic oxide produced by endothelial cells (endothelial-derived nitric oxi de, or EDNO) within large venules could act to dilate arterioles. Meth ods: 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 r ubbing technique. Venular endothelium remained intact. Endothelial den udation 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 approxi mately 50% with norepinephrine (10(-10) mol/L). Results: Topical appli cations of acetylcholine (10(-6) mol/L) or bradykinin (10(-9) mol/L) d uring luminal per fusion from venule to arteriole produced significant arteriolar dilation. In contrast, a slight arteriolar constriction wa s observed when the direction of flow was reversed (i.e., arteriole to venule) in the presence of either acetylcholine (10(-6) mol/L) or bra dykinin (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 ar teriolar dilation observed in response to acetylcholine or bradykinin during venule to arteriole perfusion. Conclusions: These results demon strate that venular-derived EDNO can relax arteriolar vascular smooth muscle.