Abushufa Adil M, Eldehni Mohamed T, Odudu Aghogho, Evans Philip D, O'Sullivan Saoirse E, McIntyre Chris W
Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Renal Medicine, Royal Derby Hospital, Derby, United Kingdom.
PLoS One. 2014 Dec 29;9(12):e113462. doi: 10.1371/journal.pone.0113462. eCollection 2014.
Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.
内皮功能障碍是慢性肾脏病（CKD）患者血管疾病的关键起始事件，而血液透析（HD）患者存在明显的血管异常。为进一步了解这一情况，我们研究了离体动脉的固有功能与HD患者心血管状态的体内评估之间的相关性。从11例HD患者和26例非尿毒症对照者获取腹部脂肪活检样本。解剖皮下动脉并安装在血管张力测定仪上，构建去甲肾上腺素、内皮素-1、血栓素A2激动剂（U46619）、血管紧张素II、血管加压素、缓激肽（BK）、乙酰胆碱（ACh）和硝普钠（SNP）的累积浓度-反应曲线。对HD患者测量脉搏波速度和血压。与对照组相比，HD患者动脉对所有收缩剂（尤其是血管加压素）的最大收缩反应（Rmax）增强（P<0.05 - 0.0001），且这种效应在内径>600 µm的动脉中更明显。HD患者内径>600 µm的动脉中，U46619（P<0.01）和血管加压素（P<0.001）的效价（pEC50）也增加。HD患者对内皮依赖性舒张剂ACh和BK的最大舒张反应较低（P<0.01 - P<0.0001）（ACh比BK更差）；然而，两组中内皮非依赖性舒张剂SNP相似。HD患者的脉搏波速度与血管加压素的血管收缩反应显著相关（P = 0.042）。HD患者因高度敏感的升压反应而易于发生高血压和终末器官需求性缺血。动脉舒张功能障碍是由内皮功能障碍介导的。固有血管异常可能在使HD患者对复发性累积性缺血性终末器官损伤敏感方面起重要作用。
