PDF(Pubmed)
Abstract：
The cholinergic pathway plays a crucial role in improving inflammatory end-organ damage. Given the interplay between cholinergic and adenosinergic neurotransmission, we tested the hypothesis that central adenosine A1 receptors (A1ARs) modulate the nicotine counteraction of cardiovascular and inflammatory insults induced by sepsis in rats. Sepsis was induced by cecal ligation and puncture (CLP) 24-h before cardiovascular measurements. Nicotine (25-100 µg/kg i.v.) dose-dependently reversed septic manifestations of hypotension and impaired heart rate variability (HRV) and cardiac sympathovagal balance. Like nicotine, intracisternal (i.c.) administration of N(6)-cyclopentyladenosine (CPA, A1AR agonist) to CLP rats increased indices of HRV and sympathovagal balance. Moreover, greater surges in these parameters were noted upon simultaneous nicotine/CPA administration. The favorable influences of nicotine on blood pressure and HRV in sepsis were diminished after central blockade of A1ARs by i.c. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). Molecular studies revealed that (i) septic rises in myocardial and brainstem nucleus of solitary tract (NTS) NFκB expression were abrogated by nicotine and largely reinstated after blockade of A1ARs, and (ii) A1AR expression in the same areas was reduced by DPCPX. It is concluded that myocardial and medullary A1ARs facilitate the cholinergic counteraction of cardiac and neuroinflammation induced by sepsis and interrelated cardiomyopathic and neuropathic hitches.
摘要：
胆碱能途径在改善炎性终末器官损伤中起关键作用。鉴于胆碱能和腺苷神经传递之间的相互作用，我们检验了以下假设:中枢腺苷A1受体(A1ARs)调节尼古丁对脓毒症大鼠引起的心血管和炎症损伤的反作用.在心血管测量前24小时，通过盲肠结扎和穿孔（CLP）诱发脓毒症。尼古丁（25-100µg/kg静脉内）剂量依赖性地逆转低血压和心率变异性（HRV）和心脏交感神经平衡的败血症表现。像尼古丁一样，脑室内（i.c.）施用N（6）-环戊基腺苷（CPA，A1AR激动剂）对CLP大鼠的HRV和交感神经平衡指数增加。此外，同时服用尼古丁/CPA后,这些参数出现了更大的波动.通过i.c.8-环戊基-1,3-二丙基黄嘌呤（DPCPX）对A1ARs进行中枢阻断后，尼古丁对脓毒症血压和HRV的有利影响减弱。分子研究表明（i）尼古丁消除了孤立道（NTS）NFκB表达的心肌和脑干核的败血症升高，并在阻断A1ARs后恢复了大部分，和（ii）DPCPX降低了相同区域中的A1AR表达。结论是，心肌和髓质A1ARs促进了胆碱能抵抗由败血症以及相关的心肌病和神经性hitches引起的心脏和神经炎症。
