Ionotropic glutamate receptors in the paraventricular nucleus (PVN) are required for sympathoexcitation due to angiotensin II (A II) in the subfornical organ (SFO) of nonpregnant and pregnant rats

Abstract

Circulating A II is increased and CNS actions of A II may support sympathetic nerve activity (SNA) in pregnancy. We previously reported greater increases in mean arterial pressure (MAP) and lumbar SNA (LSNA) in response to AT1 receptor activation in the SFO in term pregnant (P) compared to nonpregnant (NP) rats. The pathway from the SFO requires AT1 receptors in the PVN. Ionotropic glutamate receptors (iGluRs) in the PVN also contribute to sympathoexcitation from the SFO and current experiments evaluated the role of iGluRs in the PVN. Responses to microinjection of A II into the SFO were tested before and after iGluR blockade (kynurenate, KYN) in the PVN. To eliminate compensatory arterial baroreflex responses, sinoaortic denervation was performed in 5 nonpregnant (NP) and 4 term pregnant (P) inactin anesthetized rats. Baseline MAP was lower in P (84±13 mmHg) compared to NP (124±11 mmHg) rats. Increases in MAP (ΔMAP: P = +16.5±3 mmHg; NP = +10±1 mmHg) and LSNA (ΔLSNA: P= 15±3%; NP= 8±1%) in response to A II (20 μM, 50 nl) in the SFO were greater in P rats. Bilateral microinjection of KYN (27 mM, 100 nl) into the PVN had minimal effects alone, but eliminated responses to activation of the SFO in both groups (ΔMAP: P= −1±1 mmHg; NP= −1±2 mmHg; ΔLSNA: P= 0±1%; NP= 1.5±1%) Thus, both iGluRs and AT1 receptors in the PVN are required for sympathoexcitation mediated by SFO A II in NP and P rats. (NIH HL 091164)