Effects of atrial natriuretic factor on cyclic nucleotides in rabbit proximal tubule.
Atrial natriuretic factor induces renal sodium excretion by several mechanisms, including inhibition of angiotensin II-stimulated sodium reabsorption in the proximal tubule. In most tissues, the action of atrial natriuretic factor involves generation of the intracellular second messenger, cyclic GMP, but in the proximal tubule the presence of this signal transduction pathway has remained controversial. We used intrarenal 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 enriched with proximal tubules or preparations of microdissected proximal tubules were incubated with atrial natriuretic factor (1 mumol/L), cyclic GMP concentrations increased significantly. Addition of angiotensin II (1 mumol/L) together with atrial natriuretic factor had no significant effect on the stimulation of cyclic GMP accumulation observed with atrial natriuretic factor alone. Neither atrial natriuretic factor nor angiotensin II altered intracellular concentrations of cyclic AMP in tubule-enriched suspensions or microdissected tubules. We conclude that cyclic GMP acts as a second messenger for atrial natriuretic factor in rabbit proximal tubule. However, we found no evidence to support the view that alterations in intracellular cyclic AMP levels are involved in the proximal tubular actions of angiotensin II and have not been able to demonstrate that interactions between cyclic AMP and cyclic GMP underlie the antagonistic effect of atrial natriuretic factor on angiotensin II-stimulated proximal sodium transport.
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Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Harris
P J
PJ
Morgan
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis*; D006152:Cyclic GMP / Q000032:analysis*; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000187:drug effects*; D011817:Rabbits; D015398:Signal Transduction; D013535:Suspensions
D013535:Suspensions; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006152:Cyclic GMP