DIFFERENTIAL DISTRIBUTION OF ALPHA(2)-ADRENOCEPTOR SUBTYPES AND MESSENGER-RNA EXPRESSION BETWEEN RENAL-CORTEX OF SALT-SENSITIVE AND SALT-RESISTANT SABRA RATS

Objective: To assess whether alterations of alpha(2)-adrenoceptor subtypes in distribution and gene expression in the renal cortex could explain the predisposition to salt-sensitivity or salt-resistance in Sabra rats. Design: Studies were performed using plasma membranes and RNA preparations from renal cortex of 8- to 10-week-old Sabra salt-sensitive (SBH) and salt-resistant (SBN) rats on a normal-sodium diet. Methods: The alpha(2)-adrenoceptor subtypes were determined by competition experiments with [H-3]-yohimbine or [H-3]-RX821002. Their gene expression was studied by RNA-directed complementary DNA synthesis followed by Taq DNA polymerase amplification. Results: Binding studies showed that alpha(2)B- and alpha(2)A-adrenoceptor subtypes represented in SBN 72 and 28% of the maximal binding capacities of the two radioligands, respectively. In contrast, only the alpha(2)B subtype was detected in the SBH rat. However, the use of guanoxabenz disclosed alpha(2)B-adrenoceptors in alpha(2)B(1) and alpha(2)B(2) subtypes. The densities of those alpha(2)B subtypes appeared to be higher in the SBH rat than in the SBN rat. Messenger RNA corresponding to alpha(2)A and alpha(2)B subtypes were found both in SBH rats and in SBN rats. The expression of the alpha(2)B subtype was permanently higher in the SBH rats than in the SBN rats. The expression of the alpha(2)A gene in the SBH rats suggests a specific SBH post-transcriptional regulation resulting in the absence of alpha(2)A-adrenoceptor. Conclusions: Differences exist in the renal cortex concerning expression and distribution of alpha(2)-adrenoceptor subtypes between SBH and SBN rats. From these differences there might result different alpha(2)-adrenoceptor-mediated renal functions in SBH and in SBN rats, which could lead to a predisposition to sensitivity or resistance to a high sodium intake.