Downregulation of renal atrial natriuretic factor receptors and receptor mRNAs during rat pregnancy.

Using renal glomeruli and papillae from virgin, pregnant (15- to 17-day), and postpartum (day 2) rats, we investigated whether the decrease in the renal effects of atrial natriuretic factor (ANF) during pregnancy is caused by a downregulation of ANF receptors. Pregnancy decreased the maximal binding of 125I-labeled ANF to guanylyl cyclase (GC)-linked ANF-GC receptors in glomeruli and papillae and increased the binding to clearance receptors (ANF-C) in glomeruli; ANF-C receptors were not detected in the papillae Ribonuclease protection assay detected mRNAs for all the three receptors in the papillae; pregnancy decreased GC-A and ANF-C but not GC-B-receptor mRNAs. Western blots revealed a decrease in GC-A receptors in the papillae of pregnant rats; GC-B-receptor protein was barely detectable. Effects of ANF on guanosine 3', 5'-cyclic monophosphate (cGMP) production by the glomeruli and papillae were decreased during pregnancy and returned to virgin levels during postpartum. It is concluded that a decrease in the renal effects of ANF during pregnancy is caused by a downregulation of renal ANF GC-A receptors and receptor-coupled cGMP production.