CVD and hypertension are leading causes of death in the United States and risks are lower in young women than aged matched men. Ovarian hormones have significant effects, both genomic and nongenomic, on the central nervous system and cardiovascular system. 3α-hydroxy-dihydroprogesterone (3α-OH-DHP), also termed allopregnanolone, is a positive modulator of gamma aminobutyric acid (GABA) receptors that facilitates chloride into the neurons possibly by increasing the opening time of channels in the rostral ventrolateral medulla (RVLM). In fluctuation with the ovarian cycle, levels of 3α-OH-DHP are elevated in pregnant animals. Heesch's experiment was performed to determine if arterial baroreflex activity and its control on lower SNA in pregnant females could be mimicked by microinjecting allopregnanolone into the RVLM to decrease mean arterial pressure (MAP) in non-pregnant females. SNA was recorded for 15 minutes after microinjections. Heesch's results suggested reduced firing of the baroreflex and less activation of RVLM cells, resulting in hypotension (decrease of blood pressure). Lower SNA was reported in pregnant females than in non-pregnant females with less sympathoexcitation of the arterial baroreflex. In addition, increased GABAergic effects were interpreted in the RVLM, lowering the excitability (action potential) of the cell and attenuating neurotransmission release of glutamate at the spinal cord. Mean arterial pressure (MAP) did not change following microinjection of either the neuroactive progesterone metabolite or inactive isomer. The effects of progesterone metabolite are most likely nongenomic (binds to membrane vs nuclear receptors) and enhance effects of GABA. In previous studies from our laboratory, the association between males and females has been further examined. The variability of ovarian hormones like estradiol and progesterone are possible explanations for decreased MAP, resulting in lower risks of CVD in premenopausal women.
-GKG
