Pregnancy decreases GABAergic inhibition of the hypothalamic paraventricular nucleus

Depressor responses to peripheral or central infusion of Angiotensin II type 1 (AT1) receptor antagonists (AT1X) are greater in pregnant (P) compared to nonpregnant (NP) animals. AT1 and ionotropic excitatory amino acid (EAA) receptors contribute to pressor responses to GABAA receptor blockade with bicuculline (Bic) in the paraventricular nucleus (PVN) of male rats. Therefore, we hypothesized that GABAergic inhibition is decreased and AT1 receptors play a greater excitatory role in the PVN of P versus NP rats. Unilateral microinjection of Bic was performed before (Bic1), after AT1X (Bic2), and after AT1X + EAA blockade (kynurenate, Kyn) (Bic3) in the PVN. Increases in mean arterial pressure (MAP: NP = 20 ± 2; P = 12 ± 2 mmHg), heart rate (HR: NP = 57 ± 6; P = 19 ± 6 beats/min) and renal sympathetic nerve activity (RSNA: NP = 70 ± 9; P = 33 ± 7%) due to Bic (Bic1) were attenuated in P rats. Responses to AT1X and Kyn alone were insignificant in both groups. In NP rats, AT1X attenuated (+ 12 ± 4 mmHg), and AT1X + Kyn further decreased the pressor response to Bic in the PVN (+ 6 ± 2 mmHg). In P rats AT1X reduced the pressor response to Bic (+ 5 ± 1 mm Hg), and Kyn had no additional effect (+ 3 ± 1 mmHg). Effects of PVN Bic to alter the autospectra of RSNA were suppressed by prior AT1X and Kyn in both groups. Thus, tonic GABAergic inhibition is decreased and the contribution of AT1 receptors in the PVN may be greater in P rats.