Laboratory of Pharmacology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Laboratory of Pharmacology, São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Psychoneuroendocrinology. 2018 Mar;89:168-176. doi: 10.1016/j.psyneuen.2018.01.010. Epub 2018 Jan 12.
The aims of the present study were to assess an interaction of corticotropin-releasing factor (CRF) neurotransmission within the bed nucleus of the stria terminalis (BNST) with local nitrergic signaling, as well as to investigate an involvement of activation of local NMDA glutamate receptor and nitric oxide (NO) signaling in control of cardiovascular responses to acute restraint stress by BNST CRF neurotransmission in rats. We observed that CRF microinjection into the BNST increased local NO release during restraint stress. Furthermore, bilateral microinjection of CRF into the BNST enhanced both the arterial pressure and heart rate increases evoked by restraint stress, but without affecting the sympathetically-mediated cutaneous vasoconstriction. The facilitation of both pressor and tachycardiac responses to restraint stress evoked by BNST treatment with CRF were completely inhibited by local pretreatment with either the selective NMDA glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase (nNOS) inhibitor Nω-Propyl-l-arginine (NPLA), the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the protein kinase G (PKG) inhibitor KT5823. Taken together, these results provide evidence that BNST CRF neurotransmission facilitates local NMDA-mediated glutamatergic neurotransmission and activates nitrergic signaling, and this pathway is involved in control of cardiovascular responses to stress.
本研究的目的是评估终纹床核（BNST）内促肾上腺皮质释放因子（CRF）神经传递与局部硝化信号之间的相互作用，以及研究 BNST CRF 神经传递对急性束缚应激心血管反应的控制中局部 NMDA 谷氨酸受体和一氧化氮（NO）信号的激活作用。我们观察到，CRF 微注射到 BNST 会增加束缚应激时的局部 NO 释放。此外，双侧 CRF 微注射到 BNST 增强了束缚应激引起的动脉压和心率增加，但不影响交感神经介导的皮肤血管收缩。BNST 用 CRF 处理后，对束缚应激引起的升压和心动过速反应的促进作用完全被局部预处理用选择性 NMDA 谷氨酸受体拮抗剂 LY235959、选择性神经元型一氧化氮合酶（nNOS）抑制剂 Nω-丙基-L-精氨酸（NPLA）、可溶性鸟苷酸环化酶（sGC）抑制剂 1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）或蛋白激酶 G（PKG）抑制剂 KT5823 抑制。总之，这些结果提供了证据表明 BNST CRF 神经传递促进了局部 NMDA 介导的谷氨酸能神经传递，并激活了硝化信号，该途径参与了对应激心血管反应的控制。
