Szereda-Przestaszewska Malgorzata, Kaczyńska Katarzyna
Laboratory of Respiratory Reflexes, PAS Medical Research Center, 5 Pawińskiego Street, 02-106 Warsaw, Poland.
Exp Physiol. 2007 Sep;92(5):953-61. doi: 10.1113/expphysiol.2007.037333. Epub 2007 May 25.
The respiratory effects resulting from stimulation of 5-HT(1A) receptors were studied in spontaneously breathing rats that were: (i) neurally intact and subsequently bilaterally vagotomized; (ii) subjected to bilateral midcervical vagotomy followed by supranodosal vagotomy; (iii) midcervically vagotomized and treated by carotid sinus/body denervation; or (iv) subjected to infra- and supranodosal vagotomy followed by pharmacological blockade of 5-HT(1A) receptors. An intravenous bolus of the 5-HT(1A) receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 10 microg kg(-1)) evoked increases in both breathing rate and tidal volume. After section of the midcervical and supranodosal vagi, 8-OH-DPAT challenge still increased the respiratory rate and tidal volume. Carotid sinus/body denervation did not reduce the augmentation of the tidal volume, but prevented the increase in breathing rate. Blockade of 5-HT(1A) receptors with intravenous doses of 1-(2-metoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine (NAN 190; 20 microg kg(-1)) abolished all respiratory effects of 8-OH-DPAT challenge. In all the neural states, 8-OH-DPAT evoked a significant fall in mean arterial blood pressure. Pretreatment with NAN 190 reduced baseline values of mean arterial pressure and prevented 8-OH-DPAT-induced hypotension. These results indicate that: (i) 8-OH-DPAT-evoked activation of 5-HT(1A) receptors increases breathing rate and tidal volume, which persists after section of the lung vagi and the nodose ganglia, but only the increase in breathing rate was abolished by carotid sinus/body denervation; and (ii) 8-OH-DPAT hyperventilatory and hypotensive responses result from the excitation of presumed 5-HT(1A) carotid receptors and the central 5-HT(1A)-expressing neurones.
在自主呼吸的大鼠中研究了刺激5-羟色胺（5-HT）1A受体所产生的呼吸效应，这些大鼠分为以下几组：（i）神经完整，随后进行双侧迷走神经切断术；（ii）先进行双侧颈中部迷走神经切断术，随后进行结上迷走神经切断术；（iii）颈中部迷走神经切断并进行颈动脉窦/体去神经支配；或（iv）进行结下和结上迷走神经切断术，随后进行5-HT1A受体的药理学阻断。静脉注射5-HT1A受体激动剂8-羟基二丙基氨基四氢萘（8-OH-DPAT，10微克/千克）可引起呼吸频率和潮气量增加。在切断颈中部和结上迷走神经后，8-OH-DPAT激发仍可增加呼吸频率和潮气量。颈动脉窦/体去神经支配并未减少潮气量的增加，但可防止呼吸频率增加。静脉注射1-（2-甲氧基苯基）-4-[4-（2-邻苯二甲酰亚胺基）丁基]哌嗪（NAN 190；20微克/千克）阻断5-HT1A受体可消除8-OH-DPAT激发产生的所有呼吸效应。在所有神经状态下，8-OH-DPAT均可引起平均动脉血压显著下降。用NAN 190预处理可降低平均动脉压的基线值，并防止8-OH-DPAT诱导的低血压。这些结果表明：（i）8-OH-DPAT激发的5-HT1A受体激活可增加呼吸频率和潮气量，在切断肺迷走神经和结状神经节后这种效应仍然存在，但只有呼吸频率的增加可被颈动脉窦/体去神经支配消除；（ii）8-OH-DPAT的过度通气和低血压反应是由假定的5-HT1A颈动脉受体和中枢表达5-HT1A的神经元兴奋所致。
