Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Bandeirantes Avenue 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Pflugers Arch. 2018 Oct;470(10):1521-1542. doi: 10.1007/s00424-018-2149-5. Epub 2018 May 29.
The ventral medial prefrontal cortex (vMPFC) facilitates the cardiac baroreflex response through N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation by neuronal NO synthase (nNOS) and soluble guanylate cyclase (sGC) triggering. Glutamatergic transmission is modulated by the cannabinoid receptor type 1 (CB) and transient receptor potential vanilloid type 1 (TRPV) receptors, which may inhibit or stimulate glutamate release in the brain, respectively. Interestingly, vMPFC CB receptors decrease cardiac baroreflex responses, while TRPV channels facilitate them. Therefore, the hypothesis of the present study is that the vMPFC NMDA/NO pathway is regulated by both CB and TRPV receptors in the modulation of cardiac baroreflex activity. In order to test this assumption, we used male Wistar rats that had stainless steel guide cannulae bilaterally implanted in the vMPFC. Subsequently, a catheter was inserted into the femoral artery, for cardiovascular recordings, and into the femoral vein for assessing baroreflex activation. The increase in tachycardic and bradycardic responses observed after the microinjection of a CB receptors antagonist into the vMPFC was prevented by an NMDA antagonist as well as by the nNOS and sGC inhibition. NO extracellular scavenging also abolished these responses. These same pharmacological manipulations inhibited cardiac reflex enhancement induced by TRPV agonist injection into the area. Based on these results, we conclude that vMPFC CB and TRPV receptors inhibit or facilitate the cardiac baroreflex activity by stimulating or blocking the NMDA activation and NO synthesis.
腹内侧前额皮质（vMPFC）通过 N-甲基-D-天冬氨酸（NMDA）受体的激活以及神经元型一氧化氮合酶（nNOS）和可溶性鸟苷酸环化酶（sGC）触发的一氧化氮（NO）形成来促进心脏压力反射反应。谷氨酸能传递受大麻素受体 1（CB）和瞬时受体电位香草醛型 1（TRPV）受体的调节，它们分别可能抑制或刺激大脑中的谷氨酸释放。有趣的是，vMPFC CB 受体降低心脏压力反射反应，而 TRPV 通道则促进它们。因此，本研究的假设是，vMPFC NMDA/NO 通路通过 CB 和 TRPV 受体在心脏压力反射活动的调节中受到调节。为了验证这一假设，我们使用雄性 Wistar 大鼠，其双侧 vMPFC 植入不锈钢引导套管。随后，将导管插入股动脉，用于心血管记录，并插入股静脉，以评估压力反射激活。将 CB 受体拮抗剂注入 vMPFC 后观察到的心动过速和心动过缓反应增加被 NMDA 拮抗剂以及 nNOS 和 sGC 抑制所阻止。NO 细胞外清除也消除了这些反应。这些相同的药理学操作抑制了 TRPV 激动剂注射到该区域引起的心脏反射增强。基于这些结果，我们得出结论，vMPFC CB 和 TRPV 受体通过刺激或阻断 NMDA 激活和 NO 合成来抑制或促进心脏压力反射活动。
