The mechanism of Na+, K+-ATPase inhibition by atrial natriuretic factor in rat renal medulla

Atrial natriuretic peptide 99-126 (ANP(99-126)) or atrial natriuretic factor (ANF) is one of the natriuretic peptides secreted by the heart atria which produces natriuresis, diuresis and vasodilation. We examined the influence of this hormone on Na+, K+-ATPase activity in rat renal medulla. We found that infusion of ANF (0.087-0.26 nmol/kg/min) caused dose-dependent inhibition of medullary Na+, K+-ATPase activity without affecting cortical Na+, K+-ATPase. This inhibition was mimicked by synthetic analogue of cyclic guanosine 3', 5' monophosphate, 8-bromo-cGMP. Inhibitors of phosphodiesterase (papaverine and IBMX) also reduced Na+, K+-ATPase activity. This enzyme was also inhibited by the activator of soluble guanylate cyclase sodium nitroprusside. The effect of ANF, sodium nitroprusside and 8-bromo-cGMP was blocked by the specific inhibitor of protein kinase G - KT5823. The inhibitor of protein phosphatases, okadaic acid mimicked the effect of ANF and if administered together with this hormone, augmented and prolonged its action. These results suggest that ANF decreases Na+, Ki-ATPase activity in renal medulla through cGMP-protein kinase G dependent mechanism.