EFFECT OF ATRIAL-NATRIURETIC-FACTOR AND FATE OF CYCLIC-GUANOSINE-MONOPHOSPHATE IN THE RAT-KIDNEY

The mechanisms whereby atrial natriuretic factor (ANF) induces natriur esis are not clarified. Here, the effects of ANF and the cGMP analogue , 8-bromo-cGMP, on Na+, K+-ATPase activity in microdissected segments from rat medullary thick ascending limb of Henle (TAL) were evaluated. ANF-induced cGMP accumulation and the cellular handling of intracellu larly produced cGMP were also investigated, by measuring the accumulat ion of extracellular cGMP in suspensions of tubules from outer medulla , enriched in TAL, and of isolated glomeruli. ANF dose-dependently inh ibited Na+. K+-ATPase activity in isolated TAL in a parallel fashion w ith increasing cGMP accumulation in OM tubules. For both parameters. p harmacological concentrations (greater than or equal to 10(-6) M) of A NF were needed to induce a significant effect. 8-Bromo-cGMP mimicked t he inhibitory effect of ANF. The increase in the intracellular cGMP le vel in response to ANF was dose-dependently reflected in the extracell ular level. This finding contrasted with that in the glomerular prepar ation, where cGMP in response to ANF accumulated entirely intracellula rly. Also in glomeruli, high (greater than or equal to 10-6 M) concent rations of ANF were needed to induce a significant effect on cGMP accu mulation. In conclusion, ANF Inhibited Na+, K+-ATPase activity in TAL and the effect was mimicked by 8-bromo-cGMP. cGMP, produced in respons e to ANF, was extruded from the tubular epithelial cells, but not from glomeruli.