Differential distribution of alpha₂-adrenoceptor subtypes and messenger RNA expression between renal cortex of salt-sensitive and salt-resistant Sabra rats

Abstract

Objective: 

To assess whether alteration of α₂-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 α₂-adrenoceptor subtypes were determined by competition experiments with [³H]-yohimbine or [³H]-RX821002. Their gene expression was studied by RNA-directed complementary DNA synthesis followed by Taq DNA polymerase amplification.

Results: 

Binding studies showed that α₂-B- and α₂A-adrenoceptor subtypes represented in SBN 72 and 28% of the maximal binding capacities of the two radioligands, respectively. In contrast, only the α₂B subtype was detected in the SBH rat. However, the use of guanoxabenz disclosed α₂B-adrenoceptors in α₂B₁ and α₂B₂ subtypes. The densities of those α₂B subtypes appeared to be higher in the SBH rat than in he SBN rat. Messenger RNA corresponding to α₂A and α₂B subtypes were found both in SBH rats and in SBN rats. The expression of the α₂B subtype was permanently higher in the SBH rats than in the SBN rats. The expression of the α₂A gene in the SBH rats suggests a specific SBH post-transcriptional regulation resulting in the absence of α₂A-adrenoceptor.

Conclusions: 

Differences exist in the renal cortex concerning expression and distribution of α₂-adrenoceptor subtypes between SBH and SBN rats. From these differences there might result different α₂-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.