EFFECTS OF ATRIAL-NATRIURETIC-FACTOR ON CYCLIC-NUCLEOTIDES IN RABBIT PROXIMAL TUBULE

Atrial natriuretic factor induces renal sodium excretion by several me chanisms, including inhibition of angiotensin II-stimulated sodium rea bsorption in the proximal tubule. In most tissues, the action of atria l natriuretic factor involves generation of the intracellular second m essenger, cyclic GMP, but in the proximal tubule the presence of this signal transduction pathway has remained controversial. We used intrar enal arterial infusion of iron oxide followed by enzymatic dispersion and magnetic separation to obtain suspensions of rabbit kidney cortex enriched with either glomeruli or proximal tubules. When suspensions e nriched with proximal tubules or preparations of microdissected proxim al tubules were incubated with atrial natriuretic factor (1 mu mol/L), cyclic GMP concentrations increased significantly. Addition of angiot ensin II (1 mu mol/L) together with atrial natriuretic factor had no s ignificant effect on the stimulation of cyclic GMP accumulation observ ed with atrial natriuretic factor alone. Neither atrial natriuretic fa ctor nor angiotensin II altered intracellular concentrations of cyclic AMP in tubule-enriched suspensions or microdissected tubules. We conc lude that cyclic GMP acts as a second messenger for atrial natriuretic factor in rabbit proximal tubule. However, we found no evidence to su pport the view that alterations in intracellular cyclic AMP levels are involved in the proximal tubular actions of angiotensin II and have n ot been able to demonstrate that interactions between cyclic AMP and c yclic GMP underlie the antagonistic effect of atrial natriuretic facto r on angiotensin II-stimulated proximal sodium transport.