REGULATION OF ARTERIOLAR TONE AND RESPONSES VIA L-ARGININE PATHWAY IN SKELETAL-MUSCLE

With in vivo television microscopy, changes in arteriolar diameter to topical administration of various vaso-active agents were examined in the absence or in the presence of N(G)-monomethyl-L-arginine (L-NMMA, topical 100-mu-M) or N(G)-nitro-L-arginine (L-NNA, 2.5-mu-M, 20-mu-l/min ia), specific inhibitors of endothelium-derived relaxing factor (EDRF) biosynthesis. In cremaster muscle arterioles (15-22-mu-m) of rats (n = 6-11), dilations to acetylcholine (1-100 ng) were significantly inhibited (60-70%) by either of the arginine analogues. This inhibition was reversed by subsequent administration of 1 mM L-arginine. Dose-dependent constriction to norepinephrine was enhanced by L-NMMA. Indomethacin treatment reduced arteriolar dilation to bradykinin (BK, 1-100 ng), which was significantly inhibited by additional administration of L-NNA. Application of L-NNA first, followed by additional indomethacin, elicited similar results. Dilations to sodium nitroprusside and adenosine were not reduced in the presence of the inhibitors. L-NMMA or L-NNA caused no change in systemic blood pressure but elicited a significant reduction in arteriolar diameter; this effect was not reversed by 1 mM L-arginine. These data demonstrate the presence of an L-arginine pathway to produce EDRF (nitric oxide) in skeletal muscle microcirculation that mediates and/or modulates arteriolar responses to vasoactive agents and could contribute to the regulation of basal vascular tone.