Role of adenosine A2A receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control
Role of adenosine A2A receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control
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DOI：
10.1016/j.taap.2011.04.014
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
Saad, Evan I.
中科院分区：
文献类型：
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作者：
El-Mas, Mahmoud M.;El-Gowilly, Sahar M.;Saad, Evan I.
压力反射功能障碍会增加吸烟者患心血管疾病的风险。鉴于腺苷能途径在压力反射控制中的重要性，我们对心脏自主神经活动的中枢腺苷能调节缺陷介导尼古丁-压力反射相互作用的假设进行了验证。建立清醒大鼠静脉注射（1 ~ 16 μ g/kg）苯肾上腺素（PE）和硝普钠（SNP）引起心率（HR）变化与血压（BP）升高或降低相关的压力反射曲线；曲线的斜率作为压力反射灵敏度（BRS）的度量。尼古丁（25和100 μ g/kg iv.）剂量依赖性地降低了BRSSNP，而对BRSPE没有影响。脑内注射尼古丁后，brsssnp也减弱。在用阿托品或心得安预处理的大鼠中观察到类似的BRSSNP减少。尼古丁和阿托品联合治疗对BRS产生了累加性抑制作用，这种作用在同时暴露于尼古丁和心得安时没有被证明。brsssnp在经8-苯基茶碱（8- pt，非选择性腺苷受体拮抗剂）、8-（3-氯苯乙烯）咖啡因（CSC， A（2A）拮抗剂）或VUF5574 （A(3)拮抗剂）处理的制剂中降低。相比之下，阻断A(1) （DPCPX）或A(2B) （alloxazine）受体或双嘧达莫抑制腺苷摄取后，brsssnp得以保存。CSC或8-PT消除了尼古丁对brsssnp的抑制作用，而其他腺苷能拮抗剂则没有作用。总之，尼古丁通过破坏腺苷A（2A）受体介导的反射性心脏交感神经兴奋的促进作用，优先损害反射性心动过速。在临床上，尼古丁对代偿性交感神经兴奋的衰减可能对下丘脑防御反应、姿势改变和心室节律等情况有害。(C) 2011爱思唯尔公司版权所有。
Baroreflex dysfunction contributes to increased cardiovascular risk in cigarette smokers. Given the importance of adenosinergic pathways in baroreflex control, the hypothesis was tested that defective central adenosinergic modulation of cardiac autonomic activity mediates the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1-16 mu g/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious rats; slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (25 and 100 mu g/kg iv.) dose-dependently reduced BRSSNP in contrast to no effect on BRSPE. BRSSNP was also attenuated after intracisternal (i.c.) administration of nicotine. Similar reductions in BRSSNP were observed in rats pretreated with atropine or propranolol. The combined treatment with nicotine and atropine produced additive inhibitory effects on BRS, an effect that was not demonstrated upon concurrent exposure to nicotine and propranolol. BRSSNP was reduced in preparations treated with i.c. 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A(2A) antagonist), or VUF5574 (A(3) antagonist). In contrast, BRSSNP was preserved after blockade of A(1) (DPCPX) or A(2B) (alloxazine) receptors or inhibition of adenosine uptake by dipyridamole. CSC or 8-PT abrogated the BRSSNP depressant effect of nicotine whereas other adenosinergic antagonists were without effect. Together, nicotine preferentially impairs reflex tachycardia via disruption of adenosine A(2A) receptor-mediated facilitation of reflex cardiac sympathoexcitation. Clinically, the attenuation by nicotine of compensatory sympathoexcitation may be detrimental in conditions such as hypothalamic defense response, posture changes, and ventricular rhythms. (C) 2011 Elsevier Inc. All rights reserved.