Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats

During baroreceptor unloading, sympathoexcitation is attenuated in near-term pregnant compared with nonpregnant rats. Alterations in balance among different excitatory and inhibitory inputs within central autonomic pathways likely contribute to changes in regulation of sympathetic outflow in pregnancy. Both baroreflex-dependent and baro-reflex-independent GABAergic inputs inhibit sympathoexcitatory neurons within rostral ventrolateral medulla (RVLM). The present experiments tested the hypothesis that influence of baro-reflex-independent GABAergic inhibition of RVLM is greater in pregnant compared with nonpregnant rats. Afferent baroreceptor inputs were eliminated by bilateral sinoaortic denervation in inactin-anesthetized rats. In pregnant compared with nonpregnant rats, baseline mean arterial pressure (MAP) was lower (pregnant = 75 +/- 6 mmHg, nonpregnant = 115 +/- 7 mmHg) and heart rate was higher (pregnant = 381 +/- 10 beats/min, nonpregnant = 308 +/- 10 beats/min). Pressor and sympathoexcitatory [renal sympathetic nerve activity, (RSNA)] responses due to bilateral GABAA receptor blockade (bicuculline, 4 mM, 100 nl) of the RVLM were greater in pregnant rats (Delta MAP: pregnant = 101 +/- 4 mmHg, nonpregnant = 80 +/- 6 mmHg; Delta RSNA: pregnant = 182 +/- 23% control, nonpregnant = 133 +/- 10% control). Unexpected transient sympathoexcitatory effects of angiotensin AT(1) receptor blockade in the RVLM were greater in pregnant rats. Although excitatory responses to bicuculline were attenuated by prior RVLM AT(1) receptor blockade in both groups, pressor responses to disinhibition of the RVLM remained augmented in pregnant rats. Increased influence of baroreflex- independent GABAergic inhibition in RVLM could contribute to suppressed sympathoexcitation during withdrawal of arterial baroreceptor input in pregnant animals.