Cardiovascular Autonomic Responses in the VCD Rat Model of Menopause: Effects of Short- and Long-Term Ovarian Failure

Abstract

After menopause, hypertension elevates the risk of cardiac diseases, one of the major causes of women's morbidity. The gradual depletion of ovarian follicles in rats, induced by 4-vinylcyclohexene diepoxide (VCD), is a model for studying the physiology of menopause. 4-Vinylcyclohexene diepoxide treatment leads to early ovarian failure (OF) and a hormonal profile comparable to menopause in humans. We have hypothesized that OF can compromise the balance between sympathetic and parasympathetic tones of the cardiovascular system, shifting toward dominance of the former. We aimed to study the autonomic modulation of heart and blood vessels and the cardiovascular reflexes in rats presenting short-term (80 days) or long-term (180 days) OF induced by VCD. Twenty-eight-day-old Wistar rats were submitted to VCD treatment (160 mg/kg, intraperitoneally) or vehicle (control) for 15 consecutive days and experiments were conducted at 80 or 180 days after the onset of treatment. Long-term OF led to an increase in the sympathetic activity to blood vessels and an impairment in the baroreflex control of the heart, evoked by physiological changes in arterial pressure. Despite that, long-term OF did not cause hypertension during the 180 days of exposure. Short-term OF did not cause any deleterious effect on the cardiovascular parameters analyzed. These data indicate that long-term OF does not disrupt the maintenance of arterial pressure homeostasis in rats but worsens the autonomic cardiovascular control. In turn, this can lead to cardiovascular complications, especially when associated with the aging process seen during human menopause.

Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men: The Multi-Ethnic Study of Atherosclerosis

“…This could be related to abnormal endothelial independent vasodilation from arterial stiffness or increased sympathetic tone that occurs in late menopause, resulting in a higher vasomotor tone. 63 In sum, our findings may further help understand the mechanisms behind the lack of benefit of HT in older postmenopausal women seen in the randomized clinical trials. 64 Our study has many strengths including using data from a high-quality large community-based multi-ethnic cohort of men and women that has been well characterized.…”

Cardiometabolic Changes in Different Gonadal Female States Caused by Mild Hyperuricemia and Exposure to a High-Fructose Diet

“…Moreover, Huber et al demonstrated in a menopausal rat model that long-term estrogen deficiency produces a dysfunction in the cardiovascular autonomic response, favoring hypertension development [ 15 ]. In addition, estrogen deficiency induces endothelium dysfunction [ 16 , 17 ]. Likewise, uric acid levels also may be associated with hypertension, which in turn has been associated with endothelial dysfunction.…”

Current Animal Model Systems for Ovarian Aging Research

“…A galactose-induced POI rat model has shown decreased fertility, ovarian weight, body weight, and follicle number, and increased atresia [ 74 , 75 ]. A 4-vinylcyclohexene diepoxide-induced model has been used to dissect the mechanisms of ovarian aging [ 76 ].…”