Damaso Enio L, Bonagamba Leni G H, Kellett Daniel O, Jordan David, Ramage Andrew G, Machado Benedito H
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
Brain Res. 2007 May 4;1144:82-90. doi: 10.1016/j.brainres.2007.01.088. Epub 2007 Jan 31.
This study evaluated the role of 5-HT7 receptors within the central nervous system in modulating cardiovascular responses to the activation of chemo-, baro- and cardiopulmonary reflexes and in the regulation of mean arterial pressure and heart rate, using intracisternal (i.c.) application of the selective 5-HT7 receptor antagonist SB-269970 in awake rats. Experiments were performed on male Wistar rats (300-320 g). At 4 days before the experiment, rats were anesthetized and placed in a stereotaxic frame implantation of a guide cannula in the direction of the cisterna magna to be used for microinjection of saline or SB-269970 (100 microg/kg). On the day before the experiments a femoral artery and vein were cannulated to record arterial pressure and heart rate and to inject drugs to activate cardiovascular reflexes, respectively. The chemo-, baro- and cardiopulmonary reflexes were activated in different experimental groups before and after i.c. injection of saline or SB-269970. The antagonism of 5-HT7 receptors reduced: (a) the pressor (50+/-4 vs. 19+/-9 mm Hg) and bradycardic (-247+/-13 vs. -69+/-27 bpm) responses to chemoreflex activation; (b) the fall in MAP (-54+/-4 vs. -20+/-6 mm Hg) and the bradycardia (-294+/-12 vs. -98+/-34 bpm) in response to cardiopulmonary reflex activation; and (c) the gain of the baroreflex (-2.3+/-0.1 to -0.9+/-0.2 bpm/mm Hg). Intracisternal application of SB-269970 increased significantly baseline MAP in those rats previously submitted to the activation of a cardiovascular reflex but in naïve rats produced no changes in the baseline MAP were observed. The fact that cardiovascular responses to all reflexes tested were attenuated by the antagonism of 5-HT7 receptors suggests that brainstem 5-HT7 receptors brainstem facilitate the processing of the autonomic responses to cardiovascular reflex activation and that a 5-HT-containing pathway to the brainstem provides a normalizing input during challenges produced by cardiovascular reflex activation which seems to be mediated by 5-HT7 receptors.
本研究通过向清醒大鼠脑池内注射选择性5-HT7受体拮抗剂SB-269970，评估中枢神经系统内5-HT7受体在调节对化学、压力和心肺反射激活的心血管反应以及平均动脉压和心率调节中的作用。实验选用雄性Wistar大鼠（300 - 320克）。在实验前4天，将大鼠麻醉并置于立体定位框架中，向小脑延髓池方向植入引导套管，用于微量注射生理盐水或SB-269970（100微克/千克）。在实验前一天，分别插入股动脉和静脉导管，用于记录动脉压和心率，并注射药物以激活心血管反射。在脑池内注射生理盐水或SB-269970前后，不同实验组激活化学、压力和心肺反射。5-HT7受体拮抗作用降低了：(a) 对化学反射激活的升压反应（50±4 vs. 19±9毫米汞柱）和心动过缓反应（-247±13 vs. -69±27次/分钟）；(b) 对心肺反射激活的平均动脉压下降（-54±4 vs. -20±6毫米汞柱）和心动过缓（-294±12 vs. -98±34次/分钟）；以及(c) 压力反射增益（-2.3±0.1至-0.9±0.2次/分钟/毫米汞柱）。在先前已激活心血管反射的大鼠中，脑池内注射SB-269970显著增加了基线平均动脉压，但在未处理的大鼠中，未观察到基线平均动脉压有变化。5-HT7受体拮抗作用减弱了对所有测试反射的心血管反应，这一事实表明脑干5-HT7受体促进了对心血管反射激活的自主反应的处理，并且一条含5-羟色胺的通向脑干的通路在心血管反射激活产生的挑战期间提供了一个正常化输入，这似乎是由5-HT7受体介导的。
