Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat.
Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat.
复制标题
DOI：
10.1152/ajpheart.01044.2008
复制
发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Takeshi Nakamura;Kazumi Kawabe;H. Sapru
中科院分区：
文献类型：
--
作者：
Takeshi Nakamura;Kazumi Kawabe;H. Sapru
尿皮质素3 （Ucn3）是促肾上腺皮质激素释放因子（CRF）肽家族的新成员，被认为是CRF2型受体（CRF2Rs）的特异性内源性配体。CRF(2)Rs在大鼠孤束核（NTS）中存在。据推测，内侧NTS （mNTS）中CRF2Rs的激活可能在心血管调节中发挥作用。这一假设在聚氨酯麻醉、人工通气的成年雄性Wistar大鼠中进行了验证。在麻醉大鼠的mNTS中微量注射（100 nl） Ucn3（0.03、0.06、0.12和0.25 mM）可引起平均动脉压（MAP分别为5.0 +/- 1.0、21.6 +/- 2.6、20.0 +/- 2.8和12.7 +/- 3.4 mmHg）和心率（HR分别为7.8 +/- 2.6、46.2 +/- 9.3、34.5 +/- 8.4和16.6 +/- 4.9次/min）的降低。在mNTS中微量注射人工脑脊液（100 nl）没有引起心血管反应。0.06 mM浓度的Ucn3诱导MAP和HR的最大降低。Ucn3对未麻醉的中collle脱脑大鼠的心血管反应相似。双侧迷走神经切开术完全消除了ucn3诱导的心动过缓。由Ucn3引起的MAP和HR的下降（0.06 mM）被应激素（1 mM，非选择性CRFR拮抗剂）和K41498 （5 mM，选择性CRF2R拮抗剂）完全阻断。在mNTS中微量注射0.06 mM的Ucn3可降低传出大内脏神经的活动。阻断mNTS中的CRF2Rs后，ucn3诱导的交感神经输出放电减少被消除。这些结果表明，将Ucn3微量注射到mNTS中，通过CRF2Rs对mNTS神经元产生兴奋作用，导致抑制和心动过缓反应。
Urocortin 3 (Ucn3) is a new member of the corticotropin-releasing factor (CRF) peptide family and is considered to be a specific and endogenous ligand for CRF type 2 receptors (CRF2Rs). The presence of CRF(2)Rs has been reported in the nucleus tractus solitarius (NTS) of the rat. It was hypothesized that the activation of CRF2Rs in the medial NTS (mNTS) may play a role in cardiovascular regulation. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of Ucn3 (0.03, 0.06, 0.12, and 0.25 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (MAP: 5.0 +/- 1.0, 21.6 +/- 2.6, 20.0 +/- 2.8, and 12.7 +/- 3.4 mmHg, respectively) and heart rate (HR: 7.8 +/- 2.6, 46.2 +/- 9.3, 34.5 +/- 8.4, and 16.6 +/- 4.9 beats/min, respectively). Microinjections of artificial cerebrospinal fluid (100 nl) into the mNTS did not elicit cardiovascular responses. Maximum decreases in MAP and HR were elicited by 0.06 mM concentration of Ucn3. Cardiovascular responses to Ucn3 were similar in unanesthetized midcollicular decerebrate rats. A bilateral vagotomy completely abolished Ucn3-induced bradycardia. The decreases in MAP and HR elicited by Ucn3 (0.06 mM) were completely blocked by astressin (1 mM; nonselective CRFR antagonist) and K41498 (5 mM; selective CRF2R antagonist). Microinjections of Ucn3 (0.06 mM) into the mNTS decreased the efferent greater splanchnic nerve activity. After the blockade of CRF2Rs in the mNTS, a Ucn3-induced decrease in the efferent sympathetic nerve discharge was abolished. These results indicate that Ucn3 microinjections into the mNTS exerted excitatory effects on the mNTS neurons via CRF2Rs, leading to depressor and bradycardic responses.