Central Noradrenergic Activity and the Cardiovascular Effects of Nitroglycerin and Amyl Nitrate
Central Noradrenergic Activity and the Cardiovascular Effects of Nitroglycerin and Amyl Nitrate
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硝酸甘油和硝酸戊酯的中枢去甲肾上腺素能活性和心血管作用
DOI：
10.1097/00005344-199205000-00020
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发表时间：
1992
影响因子：
3
通讯作者：
J. P. Long
中科院分区：
文献类型：
--
作者：
Shengxing Ma;J. P. Long
摘要：麻醉后的Sprague-Dawley大鼠经脑室内和静脉注射硝酸甘油后，平均动脉压呈剂量依赖性降低，心率升高，但经脑室内注射硝酸甘油可引起低血压和心动过缓。脑内注射硝酸甘油的降压反应表明，该化合物的效力是静脉注射的两到三倍（当比较曲线下面积时是六倍）。静脉注射硝普钠可产生剂量依赖性的降压和心动过速效应，但通过体外注射和腹腔注射诱导的反应最小。育亨宾或月桂碱的中心预处理可拮抗静脉滴注和硝酸甘油的降压反应，但不能改变静脉滴注硝普钠诱导的降压反应。硝酸甘油静脉滴注引起的心动过速反应大于静脉滴注引起的反应。吸入亚硝酸盐戊酯可产生明显的降压反应，剂量-反应曲线右移的是经静脉滴注预处理的紫杉醇，而非静脉滴注预处理。脑脊液中3,4-二羟基苯基乙二醇和3-甲氧基-4-羟基苯基乙二醇的浓度通过静脉注射、体外注射和脑内注射硝酸甘油而升高，但静脉注射硝普钠没有改变。硝酸甘油静脉注射和体外循环注射均可提高二羟基苯乙酸的浓度。结果表明，硝酸甘油刺激中枢去甲肾上腺素能活性，这可能参与药物降压作用的组成部分。对硝酸甘油的反射性心动过速反应可因前脑刺激和髓质介导的心动过缓而进一步复杂化。硝普钠没有中枢活性
Summary: Intracerebroventricular and i.v. administration of nitroglycerin in anesthetized Sprague-Dawley rats produced dose-dependent decreases in mean arterial pressure and increases in heart rate, but intracisternal injection of the drug induced hypotension and bradycardia. Hypotensive responses to intracisternal injection of nitroglycerin showed that the compound was two to three times more potent than by i.v. administration (six times when comparing the area under the curve). Intravenous sodium nitroprusside produced dose-dependent hypotensive and tachycardiac effects, but minimal responses were induced by i.c.v. and intracisternal injection. Central pretreatment with either yohimbine or rauwolscine antagonized hypotensive responses to i.c.v. and i.v. nitroglycerin, but did not alter the depressor responses induced by i.v. sodium nitroprusside. Tachycardiac responses to i.c.v. nitroglycerin are greater than the responses induced by i.v. administration. Inhalation of amyl nitrite produced marked hypotensive responses, with the dose-response curves being shifted to the right by i.c.v. pretreatment with rauwolscine, but not by i.v. pretreatment. The concentrations of 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in cerebrospinal fluid were increased by i.v., i.c.v., and intracisternal administration of nitroglycerin, but were not altered by i.v. sodium nitroprusside. The concentrations of dihydroxyphenylacetic acid were elevated by i.v. and i.c.v. injection of nitroglycerin. Results suggest that nitroglycerin stimulates central noradrenergic activity, which may be involved in the component of hypotensive effects of the drug. Reflex tachycardiac responses to nitroglycerin may be further complicated by forebrain stimulation and medulla-mediated bradycardia. Sodium nitroprusside did not demonstrate central activity