Menezes Thiago N, Naumann Gustavo B, Peixoto Pollyana, Rouver Wender N, Gomes Helena L, Campos Fabiana V, Borges Marcia H, Dos Santos Roger L, Bissoli Nazaré S, Sanchez Eladio F, Figueiredo Suely G
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, 29043-900, Vitória, ES, Brazil.
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Maruípe, 29043-900, Vitória, ES, Brazil; Diretoria do Centro de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Rua Conde Pereira Carneiro 80, Gameleira, 30510-010, Belo Horizonte, MG, Brazil.
Toxicon. 2020 Oct 15;185:5-14. doi: 10.1016/j.toxicon.2020.06.007. Epub 2020 Jun 20.
Cardiovascular effects induced by snake venoms, in spite of having a crucial role in the outcome of the envenomation, have been less studied than other toxic activities displayed by these venoms. In this study we evaluated acute cardiovascular responses to Bothrops leucurus venom - Bl-V - both in vivo, in anesthetized rats, and in vitro, in isolated rat mesenteric resistance arteries. Bl-V (10-100 μg protein/kg) caused dose-dependent hypotension, followed by gradual recovery (2-20 min) to basal levels, and induced dose-dependent (1-20 μg/mL) vasodilation in pre-contracted arteries, what was more pronounced when the endothelium remained intact. These effects were partially counteracted by pre-treatment with indomethacin (cyclooxygenase inhibitor). Prior incubation of Bl-V with commercial pentavalent Bothrops antivenom also attenuated the cardiovascular effects induced by the venom, in spite of it not being among the venoms used for the development of the bothropic antivenom. Through an approach based on two chromatographic steps and mass spectrometry (MALDI-ToF and MALDI-ISD), a component with acute cardiovascular effects was isolated and identified as the basic phospholipase blD-PLA, previously purified from the venom of B. leucurus. Taken together, our results show that, at low doses, the venom of B. leucurus induces transient, acute hypotension in anesthetized rats following systemic vasodilation in a dose-dependent way. In addition, we provide clear evidence of the involvement of the enzymatic activity of blD-PLA in this cardiovascular response, acting via the production of vasodilating prostanoids.
尽管蛇毒引起的心血管效应在中毒后果中起着关键作用，但与这些蛇毒表现出的其他毒性活动相比，对其研究较少。在本研究中，我们评估了麻醉大鼠体内和离体大鼠肠系膜阻力动脉体外对白唇矛头蝮蛇毒（Bl-V）的急性心血管反应。Bl-V（10-100μg蛋白质/kg）引起剂量依赖性低血压，随后逐渐恢复（2-20分钟）至基础水平，并在预收缩动脉中诱导剂量依赖性（1-20μg/mL）血管舒张，当内皮保持完整时这种作用更明显。这些效应被吲哚美辛（环氧化酶抑制剂）预处理部分抵消。尽管商业五价矛头蝮抗蛇毒血清不是用于开发矛头蝮抗蛇毒血清的蛇毒之一，但将Bl-V与该抗蛇毒血清预先孵育也减弱了蛇毒诱导的心血管效应。通过基于两步色谱和质谱（基质辅助激光解吸电离飞行时间质谱和基质辅助激光解吸电离离子淌度质谱）的方法，分离并鉴定出一种具有急性心血管效应的成分，为先前从白唇矛头蝮蛇毒中纯化的碱性磷脂酶blD-PLA。综上所述，我们的结果表明，低剂量时，白唇矛头蝮蛇毒在全身血管舒张后以剂量依赖性方式诱导麻醉大鼠出现短暂的急性低血压。此外，我们提供了明确证据，证明blD-PLA的酶活性通过产生血管舒张性前列腺素参与了这种心血管反应。
