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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri

Submitted 23 May 2007 ; accepted in final form 19 September 2007

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 baroreflex-independent GABAergic inputs inhibit sympathoexcitatory neurons within rostral ventrolateral medulla (RVLM). The present experiments tested the hypothesis that influence of baroreflex-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 GABA_A receptor blockade (bicuculline, 4 mM, 100 nl) of the RVLM were greater in pregnant rats (MAP: pregnant = 101 ± 4 mmHg, nonpregnant = 80 ± 6 mmHg; RSNA: pregnant = 182 ± 23% control, nonpregnant = 133 ± 10% control). Unexpected transient sympathoexcitatory effects of angiotensin AT₁ receptor blockade in the RVLM were greater in pregnant rats. Although excitatory responses to bicuculline were attenuated by prior RVLM AT₁ 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.

sympathetic nerve activity; brain stem; cardiovascular regulation; angiotensin II