Endothelium-dependent pulmonary artery vasorelaxation is dysfunctional in males but not females after acute lung injury.

Endothelium-dependent pulmonary artery vasorelaxation is dysfunctional in males but not females after acute lung injury.
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急性肺损伤后,内皮依赖性肺动脉血管舒张功能在男性中出现功能障碍,但在女性中则不然。

DOI:
10.1016/j.surg.2005.03.002
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发表时间:
2005
期刊:
Surgery.
影响因子:
--
通讯作者:
Meldrum,DanielR
Meldrum,DanielR
中科院分区:
--
文献类型:
--
作者:
Tsai,BenM;Wang,Meijing;Pitcher,JeffreyM;Kher,Ajay;Brown,JohnW;Meldrum,DanielR

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急性呼吸窘迫综合征后的死亡率男性高于女性。肺血管反应性和局部炎症反应的性别差异可以解释这种差异。我们假设男性内皮依赖性肺血管舒张功能受损,这种效应与肺血管局部炎性细胞因子表达的差异有关。(每组n=12-16)从用内毒素处理的成年雄性和雌性Sprague-Dawley大鼠中分离(鼠伤寒沙门氏菌脂多糖,20 mg/kg IP)或媒介物(0.9%生理盐水),并连接至力传感器以测量等长力位移。绘制了内皮依赖性血管扩张剂乙酰胆碱和内皮非依赖性血管扩张剂硝普钠的剂量-反应曲线(0.01-10 μmol/L)。PA环还评估了诱导型一氧化氮合酶,肿瘤坏死因子-α,RT-PCR法检测PA和IL-1β mRNA的表达,结果表明,内毒素对PA的最大收缩无影响(564.4 ± 37.37 mg vs 633.3 ± 54.67 mg溶剂)或雌性(446.3 ± 20.00 mg vs 444.2 ± 33.02 mg溶剂),但雄性动物的内皮依赖性血管舒张显著降低(47.49 ± 5.63% vs 77.61 ± 9.41%溶剂)。内毒素血症期间,非内皮依赖性血管舒张功能保持完整。内毒素使PA诱导型一氧化氮合酶mRNA表达增加,但无性别差异。PA肿瘤坏死因子的表达没有变化,而内毒素血症的男性,但不是女性,白细胞介素1β mRNA增加,与vehicle.CONCLUSIONSThese结果表明,败血症引起的血管功能障碍男性和女性之间的不同,因此,治疗急性肺损伤可能需要性别特异性治疗。
BACKGROUNDMortality after acute respiratory distress syndrome is higher in males than in females. Gender differences in pulmonary vascular reactivity and local inflammatory response may explain this disparity. We hypothesized that endothelium-dependent pulmonary vasorelaxation is impaired in males and that this effect is related to differences in local inflammatory cytokine expression from the pulmonary vasculature.METHODSPulmonary artery (PA) rings (n=12-16 per group) were isolated from adult male and female Sprague-Dawley rats treated with endotoxin (Salmonella typhimurium lipopolysaccharide, 20 mg/kg IP) or vehicle (0.9% normal saline), and connected to force transducers for measurement of isometric force displacement. Dose-response curves (0.01-10 μmol/L) to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside were generated. PA rings were also evaluated for inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin 1β messenger RNA (mRNA) by reverse transcriptase-polymerase chain reaction.RESULTSEndotoxin had no effect on the maximum PA contraction in males (564.4 ± 37.37 mg vs 633.3 ± 54.67 mg vehicle) or females (446.3 ± 20.00 mg vs 444.2 ± 33.02 mg vehicle), but endothelium-dependent vasodilation was significantly decreased in males (47.49 ± 5.63% vs 77.61 ± 9.41% vehicle). Endothelium-independent vasodilation remained intact during endotoxemia. Endotoxin increased the PA expression of inducible nitric oxide synthase mRNA, but there was no gender difference. There was no change in expression of PA tumor necrosis factor, whereas endotoxemic males, but not females, had increased interleukin 1β mRNA, compared with vehicle.CONCLUSIONSThese results suggest that sepsis-induced vascular dysfunction differs between males and females, and, therefore, treatment of acute lung injury may require gender-specific therapies.
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