SEX DIFFERENCES IN BLOOD PRESSURE RESPONSE TO CONTINUOUS ANG II INFUSION: ARE ONLY SEX HORMONES TO BLAME?

To investigate the involvement of the sex chromosome complement (SCC), organizational and activational hormonal effects in changes in mean arterial pressure during acute Ang II infusion, we used gonadectomized (GDX) mice of the "four core genotypes" model, which dissociates the effect of gonadal sex and SCC, allowing comparisons of sexually dimorphic traits between XX and XY females as well as XX and XY males. Additionally, β-estradiol and testosterone propionate (2ug/g) were daily injected for 4 days to evaluate activational hormonal effects. Statistical analysis of the changes in mean arterial pressure revealed an interaction of SCC, organizational and activational hormonal effects during Ang II infusion {F(7,39=2,60 p<0.01)}. Our results indicate that, in absence of activational hormonal effects, interaction between the SCC and organizational hormonal action differentially modulates changes in arterial pressure. In GDX mice without hormone replacement, Ang II infusion resulted in an increase in mean arterial pressure in XX-male, XX-female and XY-female mice, while no changes were observed in XY-male mice. Furthermore, β-estradiol replacement (GDX+E2 group) resulted in a decrease in blood pressure in XX-males, XX-females and XY-females (indicating an activational β-estradiol effect), while no changes were observed in the XY-male group. Moreover, testosterone propionate replacement (GDX+TP group) showed a greater increase in blood pressure in XY-male mice than in XX-males and XX-females, demonstrating an activational hormonal effect of testosterone in XY-male mice. Our data isolates and highlights the contribution and interaction of SCC, activational and organizational hormonal effects in sex differences in Ang II blood pressure regulation.