Renal .ALPHA.2-Adrenoceptor Overexpression in Dahl Salt-Sensitive Rats. Regulation by Dietary NaCl and Dissociation from Salt-Insensitive Hypertension.

Abstract

Dietary NaCl-induced changes in blood pressure and agonist and antagonist binding properties to renal α2-adrenoceptors were studied in inbred (Rapp) strains of Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats were placed on either salt-deficient (0.13% NaCl in chow) or high salt (1% NaCl solution to drink plus 0.13% NaCl chow) diets for 1 to 8 weeks. Saturation binding studies with [3H]-rauwolscine and [3H]-p-aminoclonidine and competition studies with [3H]-rauwolscine and epinephrine were then performed in renal plasma membranes from each group. Systolic blood pressure rose significantly in S rats on the salt-deficient diet for 2 or more weeks, and was further increased by high salt intake, indicating that there are salt-sensitive and salt-insensitive components to the hypertension in inbred S rats. The blood pressure of R rats was unaffected by dietary NaCl content. Two or more weeks of high salt feeding significantly elevated renal α2-adrenoceptor density ([3H]-rauwolscine binding) in S but not R rats. Interestingly, NaCl restriction in weanling S rats completely prevented this increase in α2-adrenoceptor density over the course of the study. The number of high affinity agonist binding sites (assessed with [3H]-p-aminoclonidine and epinephrine displacement of [3H]-rauwolscine) was increased in S rats after high salt feeding. Removal of the high salt diet failed to reverse the NaCl-induced elevations in total and high affinity α2-adrenoceptor density in S rats. We conclude that: 1) the initiation of renal α2-adrenoceptor overexpression in Dahl S rats is entirely dependent on dietary NaCl content; 2) the overexpression of renal α2-adrenoceptors was independent of the salt-insensitive component of hypertension in S rats, precluding a causal linkage between these parameters; 3) the rise in renal α2-adrenoceptors was closely paralleled by salt-sensitive increments in blood pressure, suggesting a functional relationship between these two variables; 4) In contrast to reported changes in renal α2-adrenoceptor properties following renal denervation, dietary NaCl augments the number of high affinity renal α2-adrenoceptor agonist binding sites in S rats but does not increase the proportion of these sites relative to total receptor number. (Hypertens Res 1992; 15: 85-92)