Hauser G J, Dayao E K, Wasserloos K, Pitt B R, Wong H R
Division of Pediatric Critical Care Medicine, Georgetown University Children's Medical Center, Washington, District of Columbia 20007, USA.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2529-35. doi: 10.1152/ajpheart.1996.271.6.H2529.
Endotoxin (lipopolysaccharide, LPS)-induced hypotension is, in part, mediated via induction of nitric oxide synthase (iNOS), release of nitric oxide, and suppression of vascular reactivity (vasoplegia). Induction of heat shock proteins (HSP) or inhibition of iNOS expression improves survival in LPS-challenged rodents. We studied the effect of induction of HSP on LPS-mediated iNOS expression and on LPS-induced vasoplegia and hypotension. Rats were treated with the HSP inducer sodium arsenite (6 mg/kg iv) or saline control. Seventeen hours later, rats were challenged intravenously with 10 mg/kg of Escherichia coli LPS O127:B8 or saline control. Arsenite pretreatment resulted in expression of HSP 70 mRNA and of HSP 70 and heme oxygenase-1 proteins, inhibition of LPS-mediated iNOS mRNA induction, reversal of the LPS-induced hyporesponsiveness to norepinephrine ex vivo in isolated mesenteric arteries, and attenuation of LPS-induced hypotension in vivo. Our data suggest that induction of HSP expression protects rats from LPS by blocking LPS-induced iNOS expression, leading to inhibition of the overproduction of nitric oxide and thereby reversing LPS-induced vasoplegia and LPS-induced hypotension.
内毒素（脂多糖，LPS）诱导的低血压部分是通过诱导一氧化氮合酶（iNOS）、释放一氧化氮以及抑制血管反应性（血管麻痹）介导的。诱导热休克蛋白（HSP）或抑制iNOS表达可提高LPS攻击的啮齿动物的存活率。我们研究了HSP诱导对LPS介导的iNOS表达以及LPS诱导的血管麻痹和低血压的影响。用HSP诱导剂亚砷酸钠（6mg/kg静脉注射）或生理盐水对照处理大鼠。17小时后，给大鼠静脉注射10mg/kg大肠杆菌LPS O127:B8或生理盐水对照。亚砷酸钠预处理导致HSP 70 mRNA以及HSP 70和血红素加氧酶-1蛋白的表达，抑制LPS介导的iNOS mRNA诱导，逆转LPS诱导的离体肠系膜动脉对去甲肾上腺素的低反应性，并减轻LPS诱导的体内低血压。我们的数据表明，诱导HSP表达通过阻断LPS诱导的iNOS表达来保护大鼠免受LPS侵害，从而抑制一氧化氮的过量产生，进而逆转LPS诱导的血管麻痹和LPS诱导的低血压。
