Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil.
Brain Res. 2021 Jan 15;1751:147195. doi: 10.1016/j.brainres.2020.147195. Epub 2020 Nov 4.
The lateral hypothalamus (LH) is a diencephalic structure that has been considered part of the central circuitry regulating the baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this hypothalamic area are poorly understood. Therefore, in the present study we investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the LH acting via local CRF and CRF receptors in cardiac baroreflex responses in unanesthetized rats. For this, the baroreflex activity was assessed using two approaches: i) the pharmacological approach via intravenous infusion of vasoactive agents, and ii) the sequence analysis technique that evaluates reflex responses during spontaneous arterial pressure variations. The sequence analysis technique indicated that LH treatment with the selective CRF receptor antagonist CP376395 decreased the baroreflex effectiveness index, whereas the selective CRF receptor antagonist antisauvagine-30 increased the reflex shortening of pulse interval during spontaneous arterial pressure decreases. However, the pharmacological approach did not indicate effect of the bilateral microinjection of either CP376395 or antisauvagine-30 into the LH in the tachycardia evoked by blood pressure decrease or the reflex bradycardia caused by blood pressure increase. Overall, these findings indicate that CRF neurotransmission within the LH controls baroreflex function during a narrow range of physiological arterial pressure variations. Besides, results provide evidence that CRF and CRF receptors in the LH oppositely modulate the spontaneous baroreflex activity through different mechanisms.
外侧下丘脑（LH）是一个间脑结构，被认为是调节压力反射功能的中枢回路的一部分。然而，这个下丘脑区域参与压力反射控制的局部神经化学机制还知之甚少。因此，在本研究中，我们研究了 LH 内的促肾上腺皮质素释放因子（CRF）神经传递作用，通过局部 CRF 和 CRF 受体在未麻醉大鼠心脏压力反射反应中的作用。为此，我们使用两种方法评估压力反射活动：i）通过静脉内输注血管活性药物的药理学方法，和 ii）评估自发动脉血压变化期间反射反应的序列分析技术。序列分析技术表明，LH 用选择性 CRF 受体拮抗剂 CP376395 处理降低了压力反射有效性指数，而选择性 CRF 受体拮抗剂 antisauvagine-30 增加了自发动脉血压降低期间脉冲间隔的反射缩短。然而，药理学方法并未表明双侧 LH 内注射 CP376395 或 antisauvagine-30 对血压降低引起的心动过速或血压升高引起的反射性心动过缓没有影响。总的来说，这些发现表明，LH 内的 CRF 神经传递在狭窄的生理动脉血压变化范围内控制压力反射功能。此外，结果提供了证据，表明 LH 内的 CRF 和 CRF 受体通过不同的机制对自发压力反射活动进行相反的调节。
