Conducted signals within arteriolar networks initiated by bioactive amino acids

Our purpose was to determine the specificity of L-arginine (L-Arg)-induced conducted signals for intra- vs. extracellular actions of L-Arg. Diameter a nd red blood cell velocities were measured for arterioles [18 +/- 1.6 (SE) mu m] in the cremaster muscle of pentobarbital sodium-anesthetized (Nembuta l, 70 mg/kg) hamsters (n = 53). Remote (conducted) responses tt ere viewed similar to 1,000 mu m upstream from the local (micropipette) application. S ix amino acids were tested: L-arginine, L-cystine, L-leucine, L-lysine, L-h istidine, and L-aspartate (100 mu M each). Only L-Arg induced a remote dila tion; L-lysine and L-aspartate had no effect, and the others each induced a significant remote constriction. There is a second conducted signal initia ted by L-arginine that preconditions the arteriolar network and upregulates a direct response of L-arginine to dilate the remote site. This was blocke d by inhibition of L-arginine uptake at the local (preconditioning) site (1 00 mu M L-histidine or 1 mM phenformin). Arginine-glycine-aspartate (100 mu M)-induced remote dilations (+3.2 +/- 0.3 mu m) mere not mimicked by a pep tide control and were prevented by antiintegrin alpha(v) monoclonal antibod y. Remote dilations were greater in animals with a higher wall shear stress for arginine-glycine-aspartate (r(2) = 0.92) but not for L-arginine (r(2) = 0.12). Thus L-arginine initiates separate conducted signals related to sy stem y+ transport, integrins, and baseline flow.