This study aims to better understand the protective role of ERα in hypertension and its vascular consequences.
Five groups of female mice were used in this study, each one lacking either estrogens (WT-OVX), ERα (ERα-KO), membrane-ERα (C451A-ERα) or ligand-dependent-transcriptional function of ERα (AF2°). Half of the mice received a chronic infusion of angiotensin II (0.5 mg/kg/d during 1 month) to induce moderate hypertension. Systolic blood pressure (SBP) and vascular structure were measured in KO mice and compared to wild-type mice (WT). Studies were performed in 5 months mice and 16 months mice in order to evaluate the impact of aging in the estrogens protection.
SBP increased by 14 mmHg (ns) in WT mice. A similar increased was observed in C451A mice (20 mmHg, ns). By contrast, SBP increased significantly more in WT-OVX mice (31 mmHg, p=0,0007), ERα-KO (45 mmHg, p<0,0001) and AF2° mice (39 mmHg, p<0,0001). Changes in vascular structure were proportional to the evolution of SBP. At this point, results obtained from aging mice were consistent with the results obtained in young mice.
Taken together, these data suggest that the protective effect of ERα against angiotensin II-induced hypertension depend on ERα gene transcription through AF2 and not membrane ERα signaling by contrast with most described vasculoprotective effects of estrogens.
The author hereby declares no conflict of interest