Endothelium-derived relaxation mediated primarily by endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is essential in the maintenance of vascular tone. However, little is known about the effects of denervation on EDRF-mediated relaxation in the microcirculation after reimplantation. Using intravital videomicroscopy in the rat cremaster model, this study assessed the effect of acute and chronic denervation of the muscle, produced by severing the genitofemoral nerve, on EDRF-mediated vasorelaxation. The results demonstrated that acetylcholine-induced EDRF relaxation (10(-6)M) significantly relieved norepinephrine-induced vasoconstriction in small arteries (40-80 microns diameter) in both the acute and chronic denervated muscles. There was no significant difference in the relaxant response between the denervated or innervated controls in each group or between the acute or chronic groups. This relaxation was prevented by methylene blue (10(-4) M). These findings suggest that EDRF-mediated relaxation in the microcirculation is not dependent on tissue innervation. Thus the use of potent endothelial dependent agonists may be of use in cases of vasospasm postreimplantation.