Perimenopause Exacerbates Hypertension In Doca-salt Rats

Blood pressure (BP) is lower in premenopausal women than in age-matched men, but after menopause BP rates and the incidence of hypertension (HTN) show opposite tendencies. The mechanisms by which fluctuating ovarian hormone environment during that period impacts the onset and development of HTN are poorly understood, and strategies to reduce HTN risk in peri- and postmenopausal females are lacking. An ovary-intact rat model of perimenopause using the chemical, 4-vinylcyclohexene diepoxide (VCD), has been developed to accelerate the natural process of slow follicular loss. Daily dosing with VCD for 15 days selectively destroys primordial and primary follicles in ovaries of mice and rats by accelerating atresia processes, thus inducing precocious perimenopause/menopause. Hypothesis: The induction of perimenopause by VCD will increase susceptibility to the development of HTN in DOCA-salt rats. Female Sprague-Dawley rats at post-natal day 28 received subcutaneous injection of VCD (160mg/kg) or corn oil (control) for 15 days. 57 days after the first injections, nephrectomy and telemetric pressure transducer implantation were performed. After 2 weeks of recovery, a 100 mg/kg DOCA silicone or placebo pellet was implanted subcutaneously. The rats that received DOCA were provided 0.9% saline during the 21 days of DOCA protocol and mean arterial pressure (MAP) was continuously evaluated. Rats were housed weekly in metabolic cages for 24 hours to measure saline intake and urine volume. After protocol completion the animals were decapitated, and blood was collected for the measurement of anti-Mullerian hormone (AMH) and estradiol (E2) by ELISA. The AMH plasma levels were reduced in the periestropause rats (VCD + DOCA, n=9) compared to oil (Oil + DOCA, n=6) confirming the VCD-induced follicular depletion. The steady state increase in MAP (day 21 of DOCA-salt) was higher in periestropause (±45.7mmHg) compared to oil (±28.6 mmHg). Urine volume was higher in periestropause rats compared to oil. No differences were observed in the saline intake between the groups. Our data demonstrate that periestropause rats showed greater susceptibility to the development of HTN in a DOCA-salt rat model.