Bernard C, Merval R, Esposito B, Tedgui A
INSERM U141 and IFR Circulation-Lariboisière, Hôpital Lariboisière, Paris, France.
Hypertension. 1998 Jun;31(6):1350-6. doi: 10.1161/01.hyp.31.6.1350.
Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS.
脓毒性休克涉及由促炎细胞因子介导的全身血管舒张。在原发性高血压中，血管功能障碍和免疫功能障碍密切相关。与正常血压对照相比，高血压动物对内毒素（脂多糖；LPS）攻击的反应尚不清楚。将年龄匹配（12周）的正常血压Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）静脉注射10mg/kg LPS。24小时时SHR的存活率明显高于WKY（分别为15只中的12只和15只中的3只；P<0.01）。注射LPS的SHR的存活与其高血压无关，因为用肼苯哒嗪治疗使血压正常化的SHR具有相似的存活率，并且通过夹闭一侧肾动脉使血压升高的WKY显示出与正常血压WKY相似的死亡率。在LPS处理的SHR和WKY中测量连续动脉压以及白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）的连续血浆水平。SHR的延迟低血压期持续时间和IL-6的全身释放均远低于WKY，而急性低血压和血浆TNF峰值相当。我们进一步在体外探索了炎症反应，结果显示LPS激活的SHR全血产生的TNF和IL-6比LPS激活的WKY全血少。我们的结果表明，SHR比WKY具有更强的抵抗内毒素休克的能力。这与其高血压无关，而是与对LPS的炎症反应减弱有关。
