ANG II-induced hypertension in the VCD mouse model of menopause is prevented by estrogen replacement during perimenopause

作者：Pollow Dennis P Jr; Romero Aleshire Melissa J; Sanchez Jessica N; Konhilas John P; Brooks Heddwen L^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2015, 309(12): R1546-R1552.

DOI：10.1152/ajpregu.00170.2015

• aquaporin-2
• glomerular hypertrophy
• collecting duct
• estrogen

Premenopausal females are resistant to the development of hypertension, and this protection is lost after the onset of menopause, resulting in a sharp increase in disease onset and severity. However, it is unknown how a fluctuating ovarian hormone environment during the transition from perimenopause to menopause impacts the onset of hypertension, and whether interventions during perimenopause prevent disease onset after menopause. A gradual transition to menopause was induced by repeated daily injections of 4-vinylcyclohexene diepoxide (VCD). ANG II (800 ng.kg(-1).min(-1)) was infused into perimeno-pausal and menopausal female mice for 14 days. A separate cohort of mice received 17 beta-estradiol replacement during perimenopause. ANG II infusion produced significantly higher mean arterial pressure (MAP) in menopausal vs. cycling females, and 17 beta-estradiol replacement prevented this increase. In contrast, MAP was not significantly different when ANG II was infused into perimenopausal and cycling females, suggesting that female resistance to ANG II-induced hypertension is intact during perimenopause. ANG II infusion caused a significant glomerular hypertrophy, and hypertrophy was not impacted by hormonal status. Expression levels of aquaporin-2 (AQP2), a collecting duct protein, have been suggested to reflect blood pressure. AQP2 protein expression was significantly downregulated in the renal cortex of the ANG II-infused menopause group, where blood pressure was increased. AQP2 expression levels were restored to control levels with 17 beta-estradiol replacement. This study indicates that the changing hormonal environment in the VCD model of menopause impacts the severity of ANG II-induced hypertension. These data highlight the utility of the ovary-intact VCD model of menopause as a clinically relevant model to investigate the physiological mechanisms of hypertension that occur in women during the transition into menopause.

• 出版日期2015-12-15