The profound hypotension in septic shock patients is difficult to treat as it is accompanied by depressed constrictor responses to α₁-adrenoceptor agonists. Bacterial lipopolysaccharide (LPS) is the main trigger for most of the cardiovascular alterations occurring in septic shock. In this study we investigated the effects of LPS exposure on vascular contractility in general and the role of Regulator of G protein Signalling (RGS) proteins in the LPS-induced vascular alterations. Exposure of rat aortic rings to various LPS concentrations (3, 10, 30 μg/ml) for 22 hours differentially affected agonist-induced contractile responses at four distinct G-protein coupled receptors (α₁-adrenoceptors, angiotensin II, serotonin and endothelin-1 receptors). While the endothelin-1-induced contraction was unaffected by LPS pre-treatment, phenylephrine- and angiotensin II-induced contraction were significantly reduced whereas serotonin-induced contraction was significantly enhanced. Concomitantly, LPS treatment increased the RGS16 mRNA expression both in aortic rings and cultured vascular smooth muscle cells (VSMCs) but not that of RGS2, RGS3, RGS4 or RGS5. The significant increase in RGS16 mRNA expression in VSMCs by LPS was time- and concentration-dependent but independent of increased inducible NO synthase (iNOS) activity. The changes in RGS16 mRNA might contribute to the differential regulation of the contractile responses to vasoconstrictors upon LPS exposure.

中文翻译：

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LPS 对血管收缩反应的影响不同：RGS16 的潜在作用？

感染性休克患者的严重低血压难以治疗，因为它伴随着对 α _{1 -}肾上腺素能受体激动剂的收缩反应减弱。细菌脂多糖 (LPS) 是感染性休克中发生的大多数心血管改变的主要触发因素。在这项研究中，我们调查了 LPS 暴露对一般血管收缩力的影响以及 G 蛋白信号转导 (RGS) 蛋白调节剂在 LPS 诱导的血管改变中的作用。大鼠主动脉环暴露于各种 LPS 浓度（3、10、30 μg/ml）22 小时，对四种不同 G 蛋白偶联受体（α ₁-肾上腺素受体、血管紧张素 II、血清素和内皮素-1 受体）。虽然内皮素 1 诱导的收缩不受 LPS 预处理的影响，但去氧肾上腺素和血管紧张素 II 诱导的收缩显着减少，而血清素诱导的收缩显着增强。同时，LPS 处理增加了主动脉环和培养的血管平滑肌细胞 (VSMC) 中 RGS16 mRNA 的表达，但不增加 RGS2、RGS3、RGS4 或 RGS5 中的 RGS16 mRNA 表达。LPS 显着增加 VSMC 中 RGS16 mRNA 的表达是时间和浓度依赖性的，但与诱导型 NO 合酶 (iNOS) 活性的增加无关。RGS16 mRNA 的变化可能有助于 LPS 暴露后对血管收缩剂的收缩反应的差异调节。