ANF inhibits Na+, K(+)-ATPase activity in the rat thick ascending limb via a cGMP-dependent mechanism, with differential cGMP extrusion between tubules and glomeruli.
High-dose ANF inhibits rat TAL Na+,K+-ATPase via cGMP in vitro; hypothesis-generating for natriuresis mechanisms, requires in vivo confirmation before clinical relevance.
The mechanisms whereby atrial natriuretic factor (ANF) induces natriuresis 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 intracellularly produced cGMP were also investigated, by measuring the accumulation of extracellular cGMP in suspensions of tubules from outer medulla, enriched in TAL, and of isolated glomeruli. ANF dose-dependently inhibited Na+, K(+)-ATPase activity in isolated TAL in a parallel fashion with increasing cGMP accumulation in OM tubules. For both parameters, pharmacological concentrations (> or = 10(-6) M) of ANF were needed to induce a significant effect. 8-Bromo-cGMP mimicked the inhibitory effect of ANF. The increase in the intracellular cGMP level in response to ANF was dose-dependently reflected in the extracellular level. This finding contrasted with that in the glomerular preparation, where cGMP in response to ANF accumulated entirely intracellularly. Also in glomeruli, high (> or = 10(-6) M) concentrations of ANF were needed to induce a significant effect on cGMP accumulation. In conclusion, ANF inhibited Na+, K(+)-ATPase activity in TAL and the effect was mimicked by 8-bromo-cGMP. cGMP, produced in response to ANF, was extruded from the tubular epithelial cells, but not from glomeruli.
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Marie‐Louise Syrén (1997) studied this question.
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