DOWN-REGULATION OF RENAL ATRIAL-NATRIURETIC-FACTOR RECEPTORS AND RECEPTOR MESSENGER-RNAS DURING RAT PREGNANCY

Using renal glomeruli and papillae from virgin, pregnant (15- to 17-da y), and postpartum (day 2) rats, we investigated whether the decrease in the renal effects of atrial natriuretic factor (ANF) during pregnan cy is caused by a downregulation of ANF receptors. Pregnancy decreased the maximal binding of I-125-labeled ANF to guanylyl cyclase (GC)-lin ked ANF-GC receptors in glomeruli and papillae and increased the bindi ng to clearance receptors (ANF-C) in glomeruli; ANF-C receptors were n ot detected in the papillae. Ribonuclease protection assay detected mR NAs for all the three receptors in the papillae; pregnancy decreased G C-A and ANF-C but not GC-B-receptor mRNAs. Western blots revealed a de crease in GC-A receptors in the papillae of pregnant rats; GC-B-recept or protein was barely detectable. Effects of ANF on guanosine 3',5'-cy clic monophosphate (cGMP) production by the glomeruli and papillae wer e decreased during pregnancy and returned to virgin levels during post partum. It is concluded that a decrease in the renal effects of ANF du ring pregnancy is caused by a downregulation of renal ANF GC-A recepto rs and receptor-coupled cGMP production.