Pregnancy decreases baroreflex gain: role of GABA in the paraventricular nucleus

Abstract

Pregnancy (P) decreases baroreflex gain (BRG) via a mechanism that includes reduced actions of insulin in the hypothalamus. However, specific brain sites and mechanisms are unclear. The paraventricular nucleus (PVN) influences BRG and contains numerous insulin receptors (IR). Because insulin is inhibitory, we hypothesized that PVN insulin increases BRG by suppression of inhibitory GABA inputs and that loss of this action during P leads to enhanced GABAergic inhibition of BRG. To test this hypothesis, we determined if PVN microinjection of bicuculline (BIC, 60 pmol), to block GABA receptors, increases BRG more in late P than in virgin (V) urethane‐anesthetized rats. P decreased (P<0.05) BRG (in bpm/mmHg: 1.9±0.2, V, n=12; 0.9±0.2, P, n=8) and AP (in mmHg: 98±4, V; 81±5, P). In both V and P rats, PVN BIC increased (P<0.05) AP (in mmHg: by 13±2, V; by 11±3, P) and BRG (in bpm/mmHg: by 2.4±0.9, V; by 0.6±0.1, P); however, the increment in BRG was less in P rats (P<0.05). Use of immunocytochemistry, to further test the hypothesis that insulin acts via inhibition of GABAergic inputs, revealed that IR are in both magnocellular and parvocellular neuronal soma in PVN regions that also contain GABAergic (GAD67) terminals. However, no evidence of colocalization of IR in GABAergic terminals was obtained. Together, these results do not support the hypothesis that P impairs BRG by reducing insulin's action to inhibit PVN GABAergic inputs.