title: Testosterone dependence of salt-induced hypertension in Sabra rats and role of renal alpha(2)-adrenoceptor subtypes.
abstract: This study investigated the importance of the male sex hormone testosterone on salt-induced hypertension, renal alpha(2)-adrenoceptor subtype distribution, and gene expression in salt-sensitive (SBH) male Sabra rats. Comparisons of blood pressure and renal alpha(2)-adrenoceptor subtype gene expression and receptor densities have been made among sham-operated rats, and gonadectomized rats treated or not with testosterone and submitted to normal or high salt diet for 6 weeks. In intact rats, only alpha(2B)-adrenoceptors were detected in this rat strain independent of the diet. In these rats, high salt diet increases blood pressure and up-regulates gene expression and density of alpha(2)-adrenoceptors. Gonadectomy abolishes the hypertensive response to salt overload, decreases gene expression and density of alpha(2B)-adrenoceptors, and prevents their salt-induced up-regulation. After gonadectomy, increased gene expression and a detectable density of alpha(2A)-adrenoceptors are observed at similar levels in normal and high salt diet. In gonadectomized rats, testosterone replacement restores salt-induced hypertension, density of renal alpha(2B)-adrenoceptors, and gene expression to the intact levels observed both under normal and high salt diet. Furthermore, the alpha(2A)-adrenoceptor subtype is not detected in these conditions. If the increase in renal alpha(2B)-adrenoceptor subtypes is indicative of the hypertensive phenotype, the presence of the alpha(2A)-adrenoceptor appears associated with a state of salt resistance in male SBH rats. In conclusion, testosterone is needed for the full expression of salt-induced hypertension in male salt-sensitive Sabra rats. Renal densities of alpha(2)-adrenoceptor subtypes are under control of the testicles and are differentially regulated by testosterone.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculté de Médecine de Paris-Ouest, Université René Descartes, Paris, France.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Khalid
authors.forename: Norelyaquine
authors.initials: N
authors.lastname: Ilhami
authors.forename: Yves
authors.initials: Y
authors.lastname: Giudicelli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Dausse
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016316:Guanfacine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D011224:Prazosin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride; D013739:Testosterone / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D016316:Guanfacine; D013739:Testosterone; D012965:Sodium Chloride; C058525:2-methoxyidazoxan; D011224:Prazosin; D019329:Idazoxan