Sex differences in blood pressure response to continuous acute Ang II infusion: are only sex hormones to blame?

The aim of our study was to dissociate sex chromosome complement (SCC), organizational and activational hormonal effects on sexually dimorphic blood pressure regulation during continuous acute Ang-II infusion and on femoral artery Agtr1b receptor gene expression. Transgenic mice of the "four core genotypes" (in which SCC, organizational and activational hormonal effects can be dissociated), were gonadectomized and then divided into (a) without hormone replacement (GDX) (b) with β-estradiol (GDX + E2), and (c) testosterone propionate replacement (GDX + TP) groups. In anesthetized mice percentage changes in blood pressure during continuous Ang-II infusion were assayed during 10 min and (b) femoral artery Agtr1b mRNA expression was evaluated. The analysis of mean arterial pressure (MAP) in response to Ang-II infusion revealed an interaction of SCC, organizational and activational-hormonal effects. In GDX mice, while no changes in MAP were observed in XY-Male/GDX mice, it resulted in an increase in XX-Male/GDX, XX-Female/GDX and XY-Female/GDX. In XX-Male/GDX + E2, XX-Female/GDX + E2, XY-Female/GDX + E2 an activational depressor β-estradiol effect was observed when compared to GDX groups. GDX + TP treated mice showed an opposite profile to that reported for GDX groups; demonstrating an activational testosterone pressor effect in XY-Male/GDX + TP. Furthermore, an activational hormonal effect on femoral artery Agtr1b gene expression was described; in which, irrespectively of biological sex and SCC, TP groups were demonstrated to show lower Agtr1b expression when compared to GDX and GDX + E2 groups. Our data may contribute to the understanding of blood pressure regulation in the complex interplay between RAS, differential SCC backgrounds, the organizational and activational sex hormonal effects.