Dept. of Neurological Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1023-30. doi: 10.1152/ajpregu.00224.2012. Epub 2012 Sep 26.
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.
尿皮质素 3（UCN3）和 CRF2 受体（CRF2R）存在于脑组织中。疑核（nAmb）是主要的脑区，为心脏提供副交感神经支配。基于这些报道，有人假设激活 nAmb 中的 CRF2R 可能会引起心脏效应。实验在麻醉、人工通气的成年雄性 Wistar 大鼠中进行。微注射 L-谷氨酸（l-GLU，5mM）用于鉴定 nAmb。不同浓度的 UCN3（0.031、0.062、0.125、0.25 和 0.5mM）微注射到 nAmb 中引起心率（HR）降低（分别为 5.3±1、22±3.3、38±4.9、45.7±2.7 和 27.3±2.3bpm）。所有微注射的体积均为 30nl。没有观察到与 HR 降低相伴的血压变化。在 nAmb 中微注射 UCN3（0.25mM；最大有效浓度）引起的心动过缓被同一部位微注射选择性 CRF2R 拮抗剂（K41498，0.5mM 和 astressin 2B，0.25mM）显著减弱（P<0.05）。双侧迷走神经切断术消除了 UCN3 引起的心动过缓反应。这些结果表明，UCN3 在 nAmb 中激活 CRF2R 引起的心动过缓是通过迷走神经介导的。已经报道 UCN 在心力衰竭和缺血/再灌注损伤中发挥心脏保护作用。在这种情况下，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。
