Kvochina Lyudmyla, Hasser Eileen M, Heesch Cheryl M
Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, Missouri 65211, USA.
Physiol Behav. 2009 May 25;97(2):171-9. doi: 10.1016/j.physbeh.2009.02.018. Epub 2009 Feb 28.
Depressor responses to peripheral or central infusion of Angiotensin II type 1 (AT(1)) receptor antagonists (AT(1)X) are greater in pregnant (P) compared to nonpregnant (NP) animals. AT(1) and ionotropic excitatory amino acid (EAA) receptors contribute to pressor responses to GABA(A) receptor blockade with bicuculline (Bic) in the paraventricular nucleus (PVN) of male rats. Therefore, we hypothesized that GABAergic inhibition is decreased and AT(1) receptors play a greater excitatory role in the PVN of P versus NP rats. Unilateral microinjection of Bic was performed before (Bic(1)), after AT(1)X (Bic(2)), and after AT(1)X + EAA blockade (kynurenate, Kyn) (Bic(3)) 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 (Bic(1)) were attenuated in P rats. Responses to AT(1)X and Kyn alone were insignificant in both groups. In NP rats, AT(1)X attenuated (+12+/-4 mmHg), and AT(1)X + Kyn further decreased the pressor response to Bic in the PVN (+6+/-2 mmHg). In P rats AT(1)X 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 AT(1)X and Kyn in both groups. Thus, tonic GABAergic inhibition is decreased and the contribution of AT(1) receptors in the PVN may be greater in P rats.
与未怀孕（NP）的动物相比，怀孕（P）动物对血管紧张素II 1型（AT(1)）受体拮抗剂（AT(1)X）外周或中枢注射的降压反应更大。在雄性大鼠室旁核（PVN）中，AT(1)和离子型兴奋性氨基酸（EAA）受体参与了荷包牡丹碱（Bic）阻断GABA(A)受体所引起的升压反应。因此，我们推测，与NP大鼠相比，P大鼠PVN中的GABA能抑制作用减弱，且AT(1)受体发挥更大的兴奋作用。在PVN中，于注射Bic之前（Bic(1)）、注射AT(1)X之后（Bic(2)）以及注射AT(1)X + EAA阻断剂（犬尿氨酸，Kyn）之后（Bic(3)）进行单侧微量注射Bic。Bic（Bic(1)）引起的平均动脉压（MAP：NP = 20±2；P = 12±2 mmHg）、心率（HR：NP = 57±6；P = 19±6次/分钟）和肾交感神经活动（RSNA：NP = 70±9；P = 33±7%）的升高在P大鼠中减弱。两组单独对AT(1)X和Kyn的反应均不显著。在NP大鼠中，AT(1)X减弱了PVN中对Bic的升压反应（+12±4 mmHg），而AT(1)X + Kyn进一步降低了该反应（+6±2 mmHg）。在P大鼠中，AT(1)X降低了对Bic的升压反应（+5±1 mmHg），Kyn无额外作用（+3±1 mmHg）。两组中，PVN注射Bic改变RSNA自谱的作用均被预先注射的AT(1)X和Kyn抑制。因此，P大鼠中紧张性GABA能抑制作用减弱，且PVN中AT(1)受体的作用可能更大。
