Ma S X, Schmid P G, Long J P
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Life Sci. 1994;55(21):1595-603. doi: 10.1016/0024-3205(94)00325-4.
In this article we review noradrenergic activities of nitroglycerin in the central and peripheral nervous systems. Nitroglycerin may cause paradoxical bradycardia and occasional life threatening hypotension in patients. Intracisternal injections and microinjections of nitroglycerin into nucleus tractus solitarii produce hypotension and bradycardia, effects which mimic the baroreflex and may involve central noradrenergic mechanisms. The drug also triggers an alpha 2-adrenoceptor-mediated sympatho-inhibition reflex through vagal afferents. Nitroglycerin mimics biological responses associated with sympathetic neuronal activity, e.g., increase in outflow of norepinephrine and its metabolites from perfused guinea pig atria, medulla-pons tissue and cerebrospinal fluid. The sympathomimetic effects of nitroglycerin are antagonized by pre-treatment with yohimbine or rauwolscine. Clinical studies and animal experiments show that hemodynamics of nitroglycerin and sodium nitroprusside are different. Nitroglycerin is lipophilic and the compounds readily enters cells to form nitric oxide, but sodium nitroprusside is very hydrophilic and the compound has difficulty crossing membranes. Thus, intravenous nitroglycerin-induced increases in central noradrenergic activation and inhibitory reflexes may account for at least some of the therapeutic actions and side effects of the drug. In contrast, minimal central responses are produced by intravenous administration of sodium nitroprusside.
在本文中，我们综述了硝酸甘油在中枢和外周神经系统中的去甲肾上腺素能活性。硝酸甘油可能会导致患者出现反常心动过缓和偶尔危及生命的低血压。向脑池内注射以及向孤束核微量注射硝酸甘油会产生低血压和心动过缓，这些效应类似于压力感受性反射，可能涉及中枢去甲肾上腺素能机制。该药物还通过迷走传入神经触发α2肾上腺素能受体介导的交感抑制反射。硝酸甘油模拟了与交感神经元活动相关的生物学反应，例如，灌注豚鼠心房、延髓 - 脑桥组织和脑脊液中去甲肾上腺素及其代谢产物的流出增加。硝酸甘油的拟交感效应可被育亨宾或萝芙木碱预处理拮抗。临床研究和动物实验表明，硝酸甘油和硝普钠的血流动力学不同。硝酸甘油具有脂溶性，该化合物易于进入细胞形成一氧化氮，但硝普钠具有很强的亲水性，该化合物难以穿过细胞膜。因此，静脉注射硝酸甘油引起的中枢去甲肾上腺素能激活增加和抑制反射可能至少部分解释了该药物的治疗作用和副作用。相比之下，静脉注射硝普钠产生的中枢反应极小。
