Department of Anesthesiology, The University of Texas Medical Branch, 601 Harborside Drive, Galveston, TX 77555-1102, USA.
Curr Vasc Pharmacol. 2013 Mar 1;11(2):208-21.
Various forms of circulatory shock (including septic shock) lead to an impairment of vascular function, which importantly contributes to the development of multiple organ failure and mortality. Such dysfunction of blood vessels consists of two principal components: vascular smooth muscle (VSM) dysfunction, and endothelial dysfunction. The VSM dysfunction (progressive, therapy-resistant loss of VSM responsiveness to vasoconstrictor catecholamines, such as noradrenaline) leads to a progressive deterioration of blood pressure in patients with circulatory shock. The endothelial dysfunction (loss of the ability of the endothelium to produce nitric oxide and other endothelium-derived factors) contributes to the impairment of microvascular blood flow, to the enhanced adhesion and activation of neutrophils and platelets, to coagulation problems, and perfusion/metabolism mismatch in the affected organs. Here we overview the vascular regulatory functions of the novel gasotransmitter hydrogen sulfide (H2S), with an emphasis on its potential role in the pathogenesis of vascular dysfunction in circulatory shock. We first review the roles of endogenously produced or exogenously administered H2S on vascular function. Next, we review the results of published studies using shock models induced by bacterial lipopolysaccharide, and by cecal ligation and puncture, a polymicrobial model of sepsis showing overproduction of H2S. Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia. In addition, we outline the potential means by which modulation of H2S (pharmacological inhibition of its biosynthesis or therapeutic donation) may affect the outcome in circulatory shock.
各种形式的循环休克（包括感染性休克）导致血管功能障碍，这对多器官衰竭和死亡率的发展有重要贡献。这种血管功能障碍包括两个主要组成部分：血管平滑肌（VSM）功能障碍和内皮功能障碍。VSM 功能障碍（渐进性、对血管收缩性儿茶酚胺（如去甲肾上腺素）的 VSM 反应性的治疗抵抗性丧失）导致循环休克患者的血压逐渐恶化。内皮功能障碍（内皮产生一氧化氮和其他内皮衍生因子的能力丧失）导致微血管血流受损、中性粒细胞和血小板的黏附和激活增强、凝血问题以及受影响器官的灌注/代谢不匹配。在这里，我们概述了新型气体递质硫化氢（H2S）的血管调节功能，重点介绍了其在循环休克血管功能障碍发病机制中的潜在作用。我们首先回顾了内源性产生或外源性给予的 H2S 对血管功能的作用。接下来，我们回顾了使用细菌脂多糖和盲肠结扎和穿刺诱导的休克模型（一种产生过多 H2S 的脓毒症多微生物模型）发表的研究结果。最后，我们总结了 H2S 可能导致休克血管功能障碍的潜在机制，并展示了 H2S 对血管反应的改变如何在内毒素血症大鼠模型中发生的例子。此外，我们概述了调节 H2S（抑制其生物合成或治疗性供体）的潜在方法，这可能会影响循环休克的结果。
