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 and red blood cell velocities were measured for arterioles [18 ± 1.6 (SE) μm] in the cremaster muscle of pentobarbital sodium-anesthetized (Nembutal, 70 mg/kg) hamsters (n = 53). Remote (conducted) responses were viewed ~1,000 μm upstream from the local (micropipette) application. Six amino acids were tested: L-arginine, L-cystine, L-leucine, L-lysine, L- histidine, and L-aspartate (100 μM each). Only L-Arg induced a remote dilation; L-lysine and L-aspartate had no effect, and the others each induced a significant remote constriction. There is a second conducted signal initiated by L-arginine that preconditions the arteriolar network and upregulates a direct response of L-arginine to dilate the remote site. This was blocked by inhibition of L-arginine uptake at the local (preconditioning) site (100 μM L-histidine or 1 mM phenformin). Arginine-glycine-aspartate (100 μM)-induced remote dilations (+3.2 ± 0.3 μm) were not mimicked by a peptide control and were prevented by anti-integrin α(v) monoclonal antibody. Remote dilations were greater in animals with a higher wall shear stress for arginine-glycine-aspartate (r² = 0.92) but not for L-arginine (r² = 0.12). Thus L-arginine initiates separate conducted signals related to system y+ transport, integrins, and baseline flow.