Effects of a high-salt diet on hepatic atrial natriuretic peptide receptor expression in dahl salt-resistant and salt-sensitive rats

Objective: To investigate the effects of a salt diet and of salt-induced hypertension on hepatic atrial natriuretic peptide (ANP) receptors in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats. Methods: DS and DR rats were maintained for 5 weeks on either normal- (0.8% w:w NaCI) or high- (8% w: w NaCI) salt diets. Blood pressures were recorded by a tail-cuff analyser and plasma ANP concentrations were determined by radioimmunoassay. ANP binding and guanylate cyclase activities in purified liver plasma membrane fractions were determined by conventional radioreceptor and enzymatic techniques. Results: DS rats exhibited higher blood pressure than DR rats on the equivalent diet and in both groups the high-salt diet significantly increased systolic blood pressures. The high-salt diet significantly reduced plasma ANP concentrations in DR rats but not DS rats. Membrane fractions from DS rats exhibited increased ANP receptor densities compared to membranes isolated from DR rats on the equivalent diet. The high-salt diet induced a significant increase in receptor density in the DS but not the DR group. The fractional displacement of [¹²⁵I]-ANP binding by the truncated, ring-deleted analogue des[QSGLG]-4, 23-ANP-NH₂ was reduced in membrane fractions isolated from DS rats maintained on the high-salt diet. There was no change in ANP receptor affinity. Increases in receptor density in DS rats were accompanied by increases in both basal and ANP-stimulated guanylate cyclase activities. Conclusions: These results indicate that plasma membrane isolated from the liver of DS rats exhibit increased expression of the guanylate cyclase-linked ANP-B (guanylate cyclase-A and/or guanylate cyclase-B) receptors over similar preparations isolated from DR rats. ANP B receptor density is further increased when DS rats are maintained on a high-salt diet.