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Centruroides margaritatus scorpion complete venom exerts cardiovascular effects through alpha-1 adrenergic receptors
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.cbpc.2020.108939
Margarita Rosa Romero-Imbachi 1 , Nelson Cupitra 2 , Karen Ángel 3 , Beatriz González 4 , Omar Estrada 4 , Juan C Calderón 2 , Jimmy Guerrero-Vargas 3 , José Beltrán 3 , Raul Narvaez-Sanchez 2
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Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified. Aim: To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system. Methods: We evaluated the in vivo effect of CmV LD50 on the mean arterial pressure (MABP), heart rate, and surface electrocardiogram in male adult normotensive Wistar rats. Ex vivo, we evaluated the vascular reactivity of rat aortic rings to increasing concentrations (1 to 60 μg/ml) of CmV using the blockers L-NAME, indomethacin, seratrodast, and prazosin. Results: In the first hour of poisoning, CmV increased the MABP. In the second hour after poisoning, the heart rate decreased as the normalized PR interval and QT corrected increased. After that, cardiovascular shock was demonstrated by a drastic fall in the MABP and signs of cardiac conduction system block. In aortic rings, CmV caused a direct vasoconstrictor effect mediated by alpha-1 adrenergic receptors and counteracted by nitric oxide. Conclusion: The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K+ channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K+ channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects.



中文翻译:


Centruroides margaritatus 蝎子完全毒液通过 α-1 肾上腺素受体发挥心血管作用



Centruroides margaritatus蝎子蜇伤在哥伦比亚很常见。然而,毒液的心血管毒性尚未明确。目的:研究C. margaritatus全毒(CmV)对小鼠心血管系统的影响及作用机制。方法:我们评估了 CmV LD50 对雄性成年正常血压 Wistar 大鼠的平均动脉压 (MABP)、心率和表面心电图的体内影响。离体,我们使用阻滞剂 L-NAME、吲哚美辛、塞曲司特和哌唑嗪评估了大鼠主动脉环对浓度增加(1 至 60 μg/ml)的 CmV 的血管反应性。结果:在中毒的第一个小时内,CmV 增加了 MABP。中毒后第二小时,心率下降,标准化 PR 间期和校正 QT 增加。此后,MABP 急剧下降和心脏传导系统阻滞迹象表明心血管休克。在主动脉环中,CmV 引起由 α-1 肾上腺素能受体介导的直接血管收缩作用,并被一氧化氮抵消。结论:直接的血管效应和可能的心脏 α-1 效应可能解释短暂性高血压和心功能的维持,而间期延长可能是由于 K +通道阻塞所致。随后,α-1途径和K +通道途径的作用汇聚,导致致命的心血管休克。这些知识有助于了解毒液影响的动态,并有助于设计解决其心血管影响的治疗方法。

更新日期:2020-11-06
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