Zhang L, Hsu C H, Robinson C P
College of Pharmacy, University of Oklahoma, Oklahoma City 73190.
Toxicol Appl Pharmacol. 1994 Nov;129(1):16-22. doi: 10.1006/taap.1994.1224.
We have previously shown that ricin, a toxic lectin from the castor bean, increases cardiac output and blood flow to the heart in rabbits in the early stage of its intoxication and causes hemorrhage and necrosis in the heart following a lethal dose. To investigate possible alterations in coronary arteries following ricin administration, their responses to serotonin (5-HT), histamine, norepinephrine (NE), and acetylcholine (ACh) were determined. Rabbits were given 0.22 microgram/kg of ricin i.v. and euthanized 48 hr later. Cumulative contractions of rabbit coronary artery rings to 5-HT and histamine were measured. Cumulative relaxations to ACh and NE were measured in rings contracted with the histamine H1 receptor agonist 2-(2-aminoethyl)pyridine. Ricin significantly increased the EC50s of contractions of rabbit coronary artery rings to 5-HT and histamine. Maximal contractions to most agonists tested were increased. The EC50 of relaxation of rabbit coronary artery to NE was decreased, although the maximal relaxations to ACh and NE were not increased to a significant extent. It is likely that in the early stage of ricin intoxication in rabbits the sum of the effects of these vasoactive agents is to reduce the vascular tone of the coronary artery and thus reduce blood pressure and, in the late stage of ricin intoxication, vasospasm of coronary artery may cause micro- and macrocirculatory collapse.
我们之前已经表明,蓖麻毒素是一种来自蓖麻子的有毒凝集素,在其中毒早期可增加兔的心输出量和心脏血流量,致死剂量后可导致心脏出血和坏死。为了研究给予蓖麻毒素后冠状动脉可能发生的变化,测定了它们对5-羟色胺(5-HT)、组胺、去甲肾上腺素(NE)和乙酰胆碱(ACh)的反应。给兔静脉注射0.22微克/千克蓖麻毒素,48小时后实施安乐死。测定兔冠状动脉环对5-HT和组胺的累积收缩情况。在与组胺H1受体激动剂2-(2-氨基乙基)吡啶收缩的环中,测定对ACh和NE的累积舒张情况。蓖麻毒素显著增加了兔冠状动脉环对5-HT和组胺收缩的半数有效浓度(EC50)。对大多数测试激动剂的最大收缩增加。兔冠状动脉对NE舒张的EC50降低,尽管对ACh和NE的最大舒张没有显著增加。很可能在兔蓖麻毒素中毒的早期,这些血管活性物质的综合作用是降低冠状动脉的血管张力,从而降低血压,而在蓖麻毒素中毒的后期,冠状动脉痉挛可能导致微循环和大循环衰竭。