Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia; Herpetological and Toxinological Research Group, Faculty of Natural, Exact and Educational Sciences, University of Cauca, Popayán, Colombia.
Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia.
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Feb;240:108939. doi: 10.1016/j.cbpc.2020.108939. Epub 2020 Nov 6.
Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified.
To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system.
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.
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.
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.
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阐明。
研究 C. margaritatus(CmV)全毒液对小鼠心血管系统的影响和作用机制。
我们评估了 CmVLD50 对雄性成年正常血压 Wistar 大鼠平均动脉压(MABP)、心率和体表心电图的体内作用。在离体实验中,我们使用 L-NAME、吲哚美辛、色曲唑和普萘洛尔等阻滞剂评估了 CmV 对大鼠主动脉环对逐渐增加浓度(1 至 60μg/mL)的血管反应性。
在中毒后的第一个小时,CmV 增加了 MABP。在中毒后第二个小时,心率下降,PR 间期和 QT 校正间期延长。之后,心血管休克表现为 MABP 急剧下降和心脏传导系统阻滞的迹象。在主动脉环中,CmV 通过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。
直接的血管和可能的心脏α-1 作用可能解释了短暂的高血压和心脏功能的维持,而间期延长可能是由于 K 通道阻断。之后,α-1 途径和 K 通道途径的作用都集中在一起,导致致命的心血管休克。这种知识可以帮助我们理解毒液作用的动态,并设计针对其心血管作用的治疗方法。