Pregnancy decreases GABAergic inhibition of the hypothalamic paraventricular nucleus.
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.
Kvochina
Lyudmyla
L
Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, Missouri 65211, USA.
Hasser
Eileen M
EM
Heesch
Cheryl M
CM
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008845:Microinjections / Q000379:methods; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D011247:Pregnancy / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013057:Spectrum Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000959:Antihypertensive Agents; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D005680:gamma-Aminobutyric Acid; C070967:L 158809; D007736:Kynurenic Acid; D001640:Bicuculline