Vol. 299, Issue 3, 928-933, December 2001

An Up-Regulation of Renal ₂A-Adrenoceptors Is Associated with Resistance to Salt-Induced Hypertension in Sabra Rats

Mostafa Khalid, Yves Giudicelli and Jean-Pierre Dausse

Department of Biochemistry and Molecular Biology, Faculté de Médecine de Paris-Ouest, Université René Descartes, Paris, France

This study investigates the incidence of high-salt diet in blood pressures, renal ₂-adrenoceptor subtypes distribution, and gene expression in salt-sensitive (SBH) and salt-resistant (SBN) Sabra rats. Comparisons have been made between SBH and SBN rats submitted to a normal or a high-salt diet for 6 weeks. Only ₂B-adrenoceptors are detected in kidneys of SBH rats, whatever the diet. In contrast, mRNA corresponding to ₂A- and ₂B-subtypes are found in this substrain. In these rats, high-salt diet increases blood pressures and up-regulates gene expression and density of only ₂B-adrenoceptors. Inversely, ₂A- and ₂B-adrenoceptors and corresponding mRNA are found in kidneys of SBN rats. In these rats, a high-salt diet does not affect blood pressures but increases gene expression and densities of both ₂A- and ₂B-adrenoceptors. If the up-regulation of renal ₂B-adrenoceptor subtypes is indicative of the hypertensive phenotype, the present study shows that this mechanism is also present in normotensive salt-resistant Sabra rats. In fact, the absence of ₂A-adrenoceptors in SBH could be responsible for the lack of adequate receptor-mediated renal functions predisposing to salt-sensitivity and consequently the development of hypertension. Conversely, the presence of this receptor in SBN rats and its up-regulation could be protective change against the increase of ₂B-adrenoceptors induced by the salt overload and could consequently be responsible for the resistance to salt-induced hypertension.