Reduced natriuresis after oral sodium load in cholestatic rats: Role of compartment volumes and ANP

The purpose of this study was to assess the participation of the atrial nat riuretic peptide (ANP)-cGMP system in electrolyte and volume handling of ch olestatic rats submitted to an acute oral sodium load. Cholestasis was indu ced by ligation and section of the common bile duct (n = 51), Control rats were sham operated (n = 56), Three weeks after surgery, 24-hr urinary volum e, sodium, potassium, cGMP and creatinine excretion were measured. Three da ys later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary exc retion was measured for 6 hr. In parallel groups of rats, plasma volume, el ectrolytes and ANP concentration, extracellular fluid volume (ECFV), and re nal medullary ANP-induced cGMP production were determined in basal conditio ns or 1 hr after oral sodium overload. As compared with controls, cholestat ic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3 .5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic, Ch olestatic rats showed higher basal excretion of sodium, potassium, and volu me than controls, but equal urinary cGMP, After the NaCl overload, cholesta tic rats showed a reduced sodium excretion but equal urinary cGMP, One hr a fter sodium overload, both groups showed hypernatremia, but whereas in cont rol rats ECFV and ANP increased (50.7 +/- 4.7 pg/ml), in cholestatic rats E CFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ ml), ANP-induced cGMP production in renal medulla was similar in cholestati c and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg), On e hr after the load, medullary cGMP production rose significantly in both g roups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1.7 fmol/m in/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.