Zonal changes of guanidine 3', 5'-cyclic monophosphate related to endothelium-derived relaxing factor in dog renal medulla.

This study was undertaken to determine the basal and the stimulated profiles of endothelium-derived relaxing factor (EDRF) production along the cortical medullary axis of the dog kidney. To this end, slices (0.5 mm thick) were obtained from six zones equally spaced along the cortical medullary axis. Zone 1 included the medullary crest, while zones 2 and 3 included the inner medulla, zone 4 the outer medulla, zones 5 and 6 the the middle and superficial cortex, respectively. The guanidine 3', 5'-cyclic monophosphate (cGMP) content (an index of EDRF production) was determined by radioimmunoassay under basal conditions and after acetylcholine (10(-5) M), bradykinin (10(-5) M) and SIN-1 (10(-4) M) stimulation. Under basal and stimulated conditions, the cGMP concentrations were highest in the midinner medulla and decreased progressively to lowest concentration in the cortex. These responses were inhibited by NG-monomethyl-L-arginine (LNMMA), a specific antagonist of EDRF synthesis. In contrast, LNMMA did not alter the stimulation of cGMP produced by SIN-1 (10(-4) M) an endothelium-independent vasodilator. This particular localization of EDRF-mediated stimulation on the midinner medulla may have a specific role in the regulation of sodium tubular reabsorption.