Chaisakul Janeyuth, Rusmili Muhamad Rusdi Ahmad, Hodgson Wayne C, Hatthachote Panadda, Suwan Kijja, Inchan Anjaree, Chanhome Lawan, Othman Iekhsan, Chootip Krongkarn
Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand.
Department of Physiology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand.
Toxins (Basel). 2017 Mar 29;9(4):122. doi: 10.3390/toxins9040122.
Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait () envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the and cardiovascular effects of venoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. venoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC = 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by venoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.
心血管效应（如心动过速、低血压和/或高血压）通常是蛇毒中毒的临床后果。据报道，马来环蛇毒液会引起心血管效应，这可能与副交感神经活动异常有关。然而，这种效应的确切机制尚未确定。在本研究中，我们调查了泰国南部（BC-S）和东北部（BC-NE）的马来环蛇毒液对心血管的影响。毒液的SDS-PAGE分析显示毒液的蛋白质谱存在一些差异。马来环蛇毒液（50μg/kg - 100μg/kg，静脉注射）在麻醉大鼠中引起剂量依赖性低血压。最高剂量导致突然低血压（第一阶段），随后平均动脉压恢复到基线水平，并在血压略有下降（第三阶段）之前出现心率下降和短暂高血压（第二阶段）。预先给予单价抗蛇毒血清可显著减轻毒液（100μg/kg，静脉注射）引起的低血压。预先给予六甲铵（10mg/kg，静脉注射）或阿托品（5mg/kg，静脉注射）可消除BC-NE毒液的突然降压作用。BC-S和BC-NE毒液（0.1μg/kg - 100μg/ml）在内皮完整的主动脉中诱导浓度依赖性舒张（EC50分别为8±1和13±3μg/mL）。预先用L-NAME（0.2mM）孵育或去除内皮后，浓度-反应曲线明显右移，表明内皮衍生的一氧化氮（NO）可能是毒液诱导主动脉舒张的原因。我们的数据表明，马来环蛇毒液引起的心血管效应可能是由于血管介质（即NO）和通过烟碱型和毒蕈碱型乙酰胆碱受体的自主适应共同作用的结果。
