Abstract
This study investigated the importance of the male sex hormone testosterone on salt-induced hypertension, renal α2-adrenoceptor subtype distribution, and gene expression in salt-sensitive (SBH) male Sabra rats. Comparisons of blood pressure and renal α2-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 α2B-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 α2-adrenoceptors. Gonadectomy abolishes the hypertensive response to salt overload, decreases gene expression and density of α2B-adrenoceptors, and prevents their salt-induced up-regulation. After gonadectomy, increased gene expression and a detectable density of α2A-adrenoceptors are observed at similar levels in normal and high salt diet. In gonadectomized rats, testosterone replacement restores salt-induced hypertension, density of renal α2B-adrenoceptors, and gene expression to the intact levels observed both under normal and high salt diet. Furthermore, the α2A-adrenoceptor subtype is not detected in these conditions. If the increase in renal α2B-adrenoceptor subtypes is indicative of the hypertensive phenotype, the presence of the α2A-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 α2-adrenoceptor subtypes are under control of the testicles and are differentially regulated by testosterone.
Footnotes
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This study was supported by grants from INSERM and the University René Descartes.
Abbreviations
- SHR
- spontaneously hypertensive rats
- SBH
- Sabra salt-sensitive
- SBN
- Sabra salt-resistant
- PCR
- polymerase chain reaction
- bp
- base pair
- RT-PCR
- reverse transcription-polymerase chain reaction
- [3H]RX821002
- (1,4-benzodioxan-2-methoxy-2-yl)-2-imidazoline
- Received July 12, 2001.
- Accepted September 19, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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