EFFECTS OF ATRIAL-NATRIURETIC-FACTOR ON THE RENIN ALDOSTERONE SYSTEM - INVIVO AND INVITRO STUDIES

We investigated the effect of high physiological plasma levels of huma n is-proportional-to atrial natriuretic factor (ANF) on renin and aldo sterone secretion in normal sodium deplete men. In short term infusion studies (2 or 8 h duration), ANF plasma levels as observed after sodi um loading (50-70 pg/ml) lowered basal renin (PRA) and aldosterone, bu t had only a marginal effect on angiotensin II-stimulated aldosterone secretion. Preliminary results of a study with long term infusion (6 d ays) of ANF during a period of dietary sodium depletion argue against a significant tonic inhibitory effect of ANF on the renin-aldosterone system in the preceding period of sodium repletion: the plasma aldoste rone response to sodium depletion was similar with and without ANF inf usion. The second messenger of ANF for the direct inhibition of aldost erone secretion from zona glomerulosa cells is still unknown. To test the hypothesis, that cGMP is the second messenger of ANF, we produced a rise in intracellular cGMP in rat and rabbit zona glomerulosa cells using the unspecific phosphodiesterase inhibitor 3-isobutyl-1-methylxa nthine (IBMX) and the more cGMP specific phosphodiesterase specific in hibitor M + B2948 (Zaprinast). Both inhibitors simulated the action of ANF in suppressing steroid secretion and elevating cGMP levels. The r esults are compatible with the view that cGMP is of importance as a se cond messenger for ANF in adrenal zona glomerulosa cells. Selective in hibition of phosphodiesterases in combination with endopeptidase inhib ition may be an interesting principle to enhance the action of endogen ous and exogeneous ANF.