Premenopausal females are resistant to the genesis development of hypertension, and this protection is lost following 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/min) was infused into peri- and menopausal female mice for 14 days. A separate cohort of mice received 17-β estradiol replacement during perimenopause. Ang II-infusion produced significantly higher systolic blood mean arterial pressures (MAP) (SBP) in menopausal vs. cycling females and 17-β 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. Similar to studies in male mice, Ang II-infusion caused a significant glomerular hypertrophy and hypertrophy was not impacted by hormonal status. Expression levels of aquaporin-2, a collecting duct protein have been suggested to reflect blood pressure. AQP2 protein expression was significantly down regulated 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-β 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.