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

Abstract

Dietary NaCI-induced changes in blood pressure and agonist and antagonist binding properties to renal a2-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% NaCI in chow) or high salt (1% NaCI solution to drink plus 0.13% NaCI chow) diets for 1 to 8 weeks. Saturation binding studies with [3H]-rauwolscine and [H]-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 NaCI content. Two or more weeks of high salt feeding significantly elevated renal a2-adrenoceptor density ([3H]-rauwolscine binding) in S but not R rats. Interestingly, NaCI restriction in weanling S rats completely prevented this increase in a2-adrenoceptor density over the course of the study. The number of hih affinity agonist binding sites (assessed with [3H] p-aminoclonidine and epinephrine displacement of [ H]-rauwolscine) was increased in S rats after high salt feeding. Removal of the high salt diet failed to reverse the NaCI-induced elevations in total and high affinity a2-adrenoceptor density in S rats. We conclude that: 1) the initiation of renal a2-adrenoceptor overexpression in Dahl S rats is entirely dependent on dietary NaCI content; 2) the overexpression of renal a2-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 a2-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 a2-adrenoceptor properties following renal denervation, dietary NaCI augments the number of high affinity renal a2-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)

Sex influence on renal alpha 2-adrenergic receptor density in the spontaneously hypertensive rat.

“…Furthermore, renal a 2 -adrenergic receptors can be upregulated or downregulated by hormones, 25 denervation, 33 and dietary salt intake. 9 Thus, an SHR female kidney may become functionally a male kidney in terms of blood pressure regulation and renal a 2 -adrenergic receptor expression when put in a male environment. During the 10-day period after transplantation, the female kidneys have enough time to functionally become male kidneys in the studies of Harrap et al 31 a 2 -Adrenergic receptors can be regenerated in only 3 days after being destroyed.…”

“…9 Each frozen kidney was thawed, decapsulated, weighed, and homogenized in 20 mL ice-cold 50 mmol/L Tris-HCl buffer containing 5 mmol/L EDTA pH 7.7. The homogenate was centrifuged at 1700 rpm for 10 minutes (A500 rotor, Du Pont).…”

“…Renal a 2 -adrenergic receptors are overexpressed in several animal models of genetic hypertension, including the spontaneously hypertensive rat (SHR), 68 Dahl salt-sensitive hypertensive rat, 9 Sabra hypertensive rat, 10 and New Zealand genetically hypertensive rat, 11 when compared with their respective normotensive control strains. The overexpression of renal a 2 -adrenergic receptors occurs as early as 3 weeks of age in SHR compared with Wistar-Kyoto (WKY) rats, an age when blood pressure is not yet different.…”

Mapping of a Dde I RELP of the .ALPHA.2-Adrenoceptor Gene and the Correlation of Genotype with Blood Pressure in the F2 Rats of SHR-WKY Cross.

“…Previous studies have demonstrated that the density of renal a2-adrenoceptors is increased in several genetically hypertensive rat models and high salt feeding further increases the density of the a2-adrenoceptors, paralleled by an increment in blood 7). Recently, studies in our laboratory suggested that the increase in the density of renal a2-adrenoceptors in Dahl salt-sensitive (S) rats ingesting a high salt diet was due to proportional increases both in the high and low affinity binding sites (20).The percentage of high affinity binding sites did not change with strain, sodium content in the diets or whether it was measured by a full agonist or a partial agonist binding (20). Therefore, the extra a2-adrenoceptors produced in S rats are expected to be fully functional.…”