Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla

Through both genomic and nongenomic actions, ovarian hormones and their metabolites have significant effects on the central nervous system to modulate a variety of regulatory systems, including the cardiovascular system. The major metabolite of progesterone, 3α-hydroxy-dihydroprogesterone, is the most potent endogenous positive modulator of GABA(A) receptors known and central nervous system levels of this progesterone metabolite fluctuate with the ovarian cycle and are elevated in pregnant animals. Pregnancy is associated with attenuated arterial baroreflex sympathoexcitation and increased tonic GABAergic inhibition of the rostral ventrolateral medulla (RVLM) likely contributes. The current experiments were performed to determine if the effects of pregnancy on arterial baroreflex control of renal sympathetic nerve activity could be mimicked by microinjection of the neuroactive progesterone metabolite into the RVLM. Compared to control values, 15 min after microinjection of 3α-hydroxy-dihydroprogesterone into the RVLM (n=10), baseline renal sympathetic nerve activity was decreased to 82% of baseline, and the range (157±10 to 131±11%) and maximum nerve activity (164±9 to 136±12%) for the arterial baroreflex curves were decreased. In contrast, microinjection of the inactive isomer, 3β-hydroxy-dihydroprogesterone into the RVLM (n=9), had no effect on baseline nerve activity or the arterial baroreflex nerve activity range or maximum. Thus, although multiple mechanisms likely contribute to pregnancy associated changes in baroreflex function, these experiments suggest that increased levels of 3α-hydroxy-dihydroprogesterone in the RVLM might contribute.