Bradycardic effects of microinjections of urocortin 3 into the nucleus ambiguus of the rat
Bradycardic effects of microinjections of urocortin 3 into the nucleus ambiguus of the rat
复制标题
DOI：
10.1152/ajpregu.00224.2012
复制
发表时间：
2012-11-01
影响因子：
2.8
通讯作者：
Sapru, Hreday N.
中科院分区：
文献类型：
--
作者：
Chitravanshi, Vineet C.;Kawabe, Kazumi;Sapru, Hreday N.
Chitravanshi VC、Kawabe K、Sapru HN。将尿皮质素 3 显微注射到大鼠疑核中的心动过缓效应。 Am J Physiol Regul Integr Comp Physiol 303：R1023-R1030，2012。首次发表于 2012 年 8 月 22 日； doi:10.1152/ajpregu.00224.2012.-脑组织中已证实存在尿皮质素 3 (UCN3) 和 CRF2 受体 (CRF2R)。疑核 (nAmb) 是为心脏提供副交感神经支配的主要大脑区域。根据这些报告，推测 nAmb 中 CRF2R 的激活可能会引起心脏效应。实验在聚氨酯麻醉、人工通气的成年雄性 Wistar 大鼠中进行。 L-谷氨酸 (L-GLU, 5 mM) 的显微注射用于鉴定 nAmb。将不同浓度的 UCN3（0.031、0.062、0.125、0.25 和 0.5 mM）显微注射到 nAmb 中会引起心率 (HR) 降低（5.3 +/- 1、22 +/- 3.3、38 +/- 4.9、45.7 +/- 2.7 和 27.3 +/- 2.3 bpm，分别）。所有显微注射的体积为30 nl。没有观察到伴随心率降低的血压变化。在同一部位微量注射选择性 CRF2R 拮抗剂（K41498，0.5 mM 和 astressin 2B，0.25 mM）可显着（P < 0.05）减弱 UCN3（0.25 mM；最大有效浓度）微量注射到 nAmb 中引起的心动过缓。双侧迷走神经切断术消除了对 UCN3 的心动过缓反应。这些结果表明，UCN3 激活 nAmb 中的 CRF2R 会引发迷走神经介导的心动过缓。据报道，UCN 对心力衰竭和缺血/再灌注损伤具有心脏保护作用。在这种情况下，由 UCN3 引起的中枢性心动过缓将是有益的。本研究的结果为未来研究 nAmb 中 CRF2R 在心力衰竭等病理状态中的作用提供了一个平台。
Chitravanshi VC, Kawabe K, Sapru HN. Bradycardic effects of microinjections of urocortin 3 into the nucleus ambiguus of the rat. Am J Physiol Regul Integr Comp Physiol 303: R1023-R1030, 2012. First published August 22, 2012; doi:10.1152/ajpregu.00224.2012.-The presence of urocortin 3 (UCN3) and CRF2 receptors (CRF2R) has been demonstrated in brain tissue. Nucleus ambiguus (nAmb) is the predominant brain area providing parasympathetic innervation to the heart. On the basis of these reports, it was hypothesized that activation of CRF2Rs in the nAmb may elicit cardiac effects. Experiments were carried out in urethane-anesthetized, artificially ventilated, and adult male Wistar rats. Microinjections of L-glutamate (L-GLU, 5 mM) were used to identify the nAmb. Different concentrations of UCN3 (0.031, 0.062, 0.125, 0.25, and 0.5 mM) microinjected into the nAmb elicited decreases in heart rate (HR) (5.3 +/- 1, 22 +/- 3.3, 38 +/- 4.9, 45.7 +/- 2.7, and 27.3 +/- 2.3 bpm, respectively). The volume of all microinjections was 30 nl. Blood pressure changes concomitant with decreases in HR were not observed. Bradycardia elicited by microinjections of UCN3 (0.25 mM; maximally effective concentration) into the nAmb was significantly (P < 0.05) attenuated by microinjections of selective CRF2R antagonists (K41498, 0.5 mM, and astressin 2B, 0.25 mM) at the same site. Bilateral vagotomy abolished the bradycardic responses to UCN3. These results indicated that activation of CRF2Rs in the nAmb by UCN3 elicited bradycardia, which was vagally mediated. UCNs have been reported to exert cardioprotective effects in heart failure and ischemia/reperfusion injury. In this situation, centrally induced bradycardia by UCN3 would be beneficial. The results of the present investigation provide a platform for future studies on the role of CRF2Rs in the nAmb in pathological states such as heart failure.