Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin.
Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin.
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DOI：
10.1152/ajpregu.00396.2013
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发表时间：
2014-05
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影响因子：
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通讯作者：
G. Yosten;W. Samson
中科院分区：
文献类型：
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作者：
G. Yosten;W. Samson
Nesfatin-1在外周和大脑中产生，在那里它已被证明可以调节食欲，应激激素分泌和心血管功能。中枢nesfatin-1的促肾上腺皮质激素作用需要募集产生黑皮质素的神经元和中枢投射催产素（OT）和促肾上腺皮质激素释放激素（CRH）神经元。我们以前已经表明，这一途径的两个组成部分，中央黑皮质素和催产素系统，有助于nesfatin-1的高血压作用。我们假设奈法汀-1的心血管作用也依赖于表达CRH受体的神经元的激活，并且黑皮质素-CRH-催产素回路的激活顺序对于该肽的厌食和高血压作用都是保留的。用CRH-2受体拮抗剂astressin 2B预处理雄性大鼠，可消除nesfatin-1诱导的平均动脉压（MAP）升高。此外，CRH的高血压作用被阻断预处理与催产素受体拮抗剂鸟氨酸vasotocin（OVT），表明nesfatin-1的高血压效应可能需要激活催产素能（OTergic）神经元，除了招募CRH神经元。有趣的是，我们发现α-黑素细胞刺激激素（α-MSH）本身的高血压作用不被astressin 2B或OVT阻断。这些数据表明，虽然产生α-MSH的神经元是调节食物摄入的核心黑皮质素-CRH-催产素回路的一部分，并且由nesfatin-1激活的黑皮质素神经元亚群确实介导了该肽的高血压作用，但α-MSH可以独立于该回路发出信号以增加MAP。
Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.