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-induc ed 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 NaCl) or high- (8% w:w NaCl) salt diets. Blood pressures were recor ded by a tail-cuff analyser and plasma ANP concentrations were determi ned by radioimmunoassay. ANP binding and guanylate cyclase activities in purified liver plasma membrane fractions were determined by convent ional radioreceptor and enzymatic techniques. Results: DS rats exhibit ed higher blood pressure than DR rats on the equivalent diet and in bo th groups the high-salt diet significantly increased systolic blood pr essures. The high-salt diet significantly reduced plasma ANP concentra tions in DR rats but not DS rats. Membrane fractions from DS rats exhi bited increased ANP receptor densities compared to membranes isolated from DR rats on the equivalent diet. The high-salt diet induced a sign ificant increase in receptor density in the DS but not the DR group. T he fractional displacement of [I-125]-ANP binding by the truncated, ri ng-deleted analogue des[QSGLG]-4,23-ANP-NH2 was reduced in membrane fr actions 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-stimula ted guanylate cyclase activities. Conclusions: These results indicate that plasma membrane isolated from the liver of DS rats exhibit increa sed expression of the guanylate cyclase-linked ANP-B (guanylate cyclas e-A and/or guanylate cyclase-B) receptors over similar preparations is olated from DR rats. ANP B receptor density is further increased when DS rats are maintained on a high-salt diet.