Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Brain Res. 2020 Nov 15;1747:147037. doi: 10.1016/j.brainres.2020.147037. Epub 2020 Jul 30.
Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3',5'-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported. Thus, the present study aimed to investigate the involvement of nitric oxide/cyclic guanosine-3',5'-monophosphate pathway mediated by neuronal nitric oxide synthase (nNOS) activation within the insular cortex in the modulation of baroreflex responses in unanesthetized rats. For this, we evaluated the effect of bilateral microinjection of either the nitric oxide scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase inhibitor N-Propyl-l-arginine or the soluble guanylate cyclase inhibitor ODQ into the insular cortex on the bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and the tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of either NPLA or carboxy-PTIO into the insular cortex increased the reflex bradycardic response, whereas the reflex tachycardia was decreased by these treatments. Bilateral microinjection of the soluble guanylate cyclase inhibitor into the insular cortex did not affect any parameter of baroreflex function evaluated. Overall, our findings provide evidence that insular cortex nitrergic signaling, acting via neuronal nitric oxide synthase, plays a prominent role in control of baroreflex function. However, control of reflex responses seems to be independent of soluble guanylate cyclase activation.
岛叶皮层是参与自主活动和心血管功能调节的脑结构。一氧化氮/环鸟苷酸 3'，5'-单磷酸途径是中枢神经系统中突出的信号机制，控制行为和生理反应。然而，尽管有证据表明岛叶皮层中存在合成一氧化氮的神经元，但它在自主和心血管功能控制中的作用从未被报道过。因此，本研究旨在探讨岛叶皮层神经元型一氧化氮合酶（nNOS）激活介导的一氧化氮/环鸟苷酸 3'，5'-单磷酸途径在调节未麻醉大鼠压力反射反应中的作用。为此，我们评估了将一氧化氮清除剂羧基-PTIO、选择性神经元型一氧化氮合酶抑制剂 N-Propyl-l-arginine 或可溶性鸟苷酸环化酶抑制剂 ODQ 双侧微注射到岛叶皮层对静脉输注去氧肾上腺素引起的血压升高时诱发的心动过缓以及静脉输注硝普钠引起的血压降低时诱发的心动过速的影响。双侧微注射 NPLA 或羧基-PTIO 到岛叶皮层增加了反射性心动过缓反应，而这些处理降低了反射性心动过速。双侧微注射可溶性鸟苷酸环化酶抑制剂到岛叶皮层对压力反射功能的任何参数均无影响。总的来说，我们的发现提供了证据，表明岛叶皮层的氮能信号，通过神经元型一氧化氮合酶起作用，在控制压力反射功能中起着重要作用。然而，反射反应的控制似乎独立于可溶性鸟苷酸环化酶的激活。
