Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
Exp Physiol. 2011 Mar;96(3):262-74. doi: 10.1113/expphysiol.2010.054882. Epub 2010 Dec 10.
Anatomical studies have demonstrated the existence of purinergic P2 receptors in the nucleus ambiguus (NA), a site containing cardiac vagal motoneurons. However, very little is known about the functional role of these receptors in central cardiac vagal regulation. The aims of our study were to evaluate the following: (1) the blood pressure and heart rate responses following purinoceptor activation within the NA; (2) the role of purinoceptors and excitatory amino acid (EAA) receptors in mediating the cardiovascular responses evoked by ATP and L-glutamate stimulation of NA; and (3) the role of NA purinoceptors in mediating the cardiovascular responses of the Bezold-Jarisch reflex. In anaesthetized rats, microinjection of L-glutamate (5.0 nmol/50 nl) into the NA induced a marked and immediate onset bradycardia with minimal change in arterial pressure. Microinjection of ATP into the NA induced a dose-dependent (0.31-6.0 nmol/50 nl) bradycardia and pressor responses. It is noteworthy that the bradycardia occurred either before or simultaneously with a pressor response (when present), indicating that it was not a baroreceptor reflex mediated response due to the rise in arterial pressure. The pressor response was prevented by α(1)-adrenergic blockade with prazosin, whereas muscarinic blockade with methyl-atropine abolished the evoked bradycardia. Ipsilateral microinjection of PPADS (a P2 receptor antagonist; 500 pmol/100 nl) into the NA significantly attenuated the ATP-induced bradycardia but spared the pressor response. In contrast, PPADS in the NA had no effect on the L-glutamate-evoked bradycardic response. Ipsilateral injection of kynurenic acid (a non-selective EAA receptor antagonist; 10 nmol/50 nl) into the NA totally blocked the bradycardia induced by l-glutamate and partly attenuated the ATP induced bradycardia. Finally, both the depressor and the bradycardic responses of the Bezold-Jarisch reflex were attenuated significantly (P < 0.01 and P < 0.05, respectively) following bilateral microinjection of PPADS into the NA. These results identify ATP and purinergic P2 receptors within the ventrolateral medulla as excitatory to cardiovagal neurons. Additionally, our data show that P2 receptors within the ventrolateral medulla are integral to the cardiovascular responses of the Bezold-Jarisch reflex.
解剖学研究表明，嘌呤能 P2 受体存在于疑核（NA）中，该部位包含心脏迷走运动神经元。然而，关于这些受体在中枢心脏迷走神经调节中的功能作用，我们知之甚少。我们的研究目的是评估以下内容：（1）嘌呤能受体在 NA 内激活后对血压和心率的影响；（2）嘌呤能受体和兴奋性氨基酸（EAA）受体在介导 NA 内 ATP 和 L-谷氨酸刺激引起的心血管反应中的作用；（3）NA 嘌呤能受体在介导 Bezold-Jarisch 反射的心血管反应中的作用。在麻醉大鼠中，将 L-谷氨酸（5.0 nmol/50 nl）微注射到 NA 中会引起明显的、立即发作的心动过缓，而动脉压仅有微小变化。将 ATP 微注射到 NA 中会引起剂量依赖性（0.31-6.0 nmol/50 nl）的心动过缓和升压反应。值得注意的是，心动过缓发生在升压反应之前或同时（如果存在），表明这不是由于动脉压升高引起的压力感受器反射介导的反应。用哌唑嗪阻断α（1）-肾上腺素能可防止升压反应，而用甲基阿托品阻断毒蕈碱可消除诱发的心动过缓。将 PPADS（一种 P2 受体拮抗剂；500 pmol/100 nl）同侧微注射到 NA 中可显著减弱 ATP 引起的心动过缓，但不影响升压反应。相比之下，PPADS 在 NA 中对 L-谷氨酸引起的心动过缓反应没有影响。将 kynurenic 酸（一种非选择性 EAA 受体拮抗剂；10 nmol/50 nl）同侧注射到 NA 中可完全阻断 L-谷氨酸引起的心动过缓，并部分减弱 ATP 引起的心动过缓。最后，双侧微注射 PPADS 到 NA 后，Bezold-Jarisch 反射的降压和心动过缓反应均显著减弱（分别为 P < 0.01 和 P < 0.05）。这些结果表明，腹外侧髓质中的 ATP 和嘌呤能 P2 受体对心脏迷走神经元具有兴奋性。此外，我们的数据表明，腹外侧髓质中的 P2 受体是 Bezold-Jarisch 反射心血管反应的组成部分。
