Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels
Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels
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DOI：
10.1093/eurheartj/ehi113
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发表时间：
2005-03-01
影响因子：
39.3
通讯作者：
Ferrannini, E
中科院分区：
文献类型：
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作者：
Natali, A;Toschi, E;Ferrannini, E
目的在2型糖尿病、高血压和吸烟等情况下，红细胞压积（Hct）往往较高，内皮功能受损。在体外，血红素能非常有效地中和一氧化氮。红细胞在体内是否参与内皮功能的调节尚不明确。方法与结果测定84例2型糖尿病患者和19例对照者的临床、血液学参数和前臂血流对乙酰胆碱（ACh）和硝普钠（SNP）的反应。糖尿病患者对SNP和乙酰胆碱的剂量反应曲线均呈钝化。在糖尿病患者中，尽管年龄、体重指数、血红蛋白（HbA(1c)）、血压、血清总胆固醇和高密度脂蛋白胆固醇水平、胰岛素敏感性指标和炎症标志物相似，但在不同四分之一的Hct组中，乙酰胆碱血流量反应逐渐升高（881 +/- 96,652 +/- 81,513 +/- 54,307 +/- 46%,P < 0.0001），最大SNP反应趋于降低（706 +/- 72,578 +/- 61,607 +/- 69,499 +/- 53%,P = 0.06）。在将ACh反应归一化为SNP反应（ACh/SNP比率）后，仍观察到Hct各组的反应逐渐降低（1.54 +/- 0.23,1.22 +/- 0.15,0.93 +/- 0.09,0.66 +/- 0.09,P < 0.0001），与对照组（1.44 +/- 0.08）相比，III和IV组的患者反应迟钝。在糖尿病患者和对照组中，ACh/SNP比值与Hct呈负相关（r = -0.46和r = -0.66, P < 0.002）。这种相关性与合并症、性别、代谢控制、血浆脂质或伴随治疗无关，在保留内皮依赖性扩张的受试者中更强，当血红蛋白取代Hct时也没有变化。结论糖尿病患者和非糖尿病患者的红细胞压积与小血管内皮依赖性扩张呈负相关。因此，除了血液流变学，对一氧化氮有效性的直接负面影响可能解释了高Hct与心血管疾病之间的联系。
Aims In conditions such as type 2 diabetes, hypertension, and smoking, in which haematocrit (Hct) tends to be higher, endothetial function is impaired. In vitro, haemogtobin neutralizes nitric oxide very effectively. Whether red blood cells participate in the regulation of endothelial function in vivo has not been established. Methods and results Clinical and haematotogical parameters and forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured in 84 type 2 diabetic patients and 19 control subjects. Diabetics showed blunted doseresponse curves to both SNP and ACh. In diabetics, across quartites of Hct, ACh blood flow responses were progressively tower (881 +/- 96, 652 +/- 81, 513 +/- 54, 307 +/- 46%, P < 0.0001), and maximal SNP responses tended to be lower (706 +/- 72, 578 +/- 61, 607 +/- 69, 499 +/- 53%, P = 0.06) despite similar age, body mass index, gtycated haemogtobin (HbA(1c)), blood pressure, serum total and HDL-chotesterot levels, indices of insulin sensitivity, and markers of inflammation. After normalizing the ACh response for the SNP response (ACh/SNP ratio), a progressive reduction across Hct quartites (1.54 +/- 0.23, 1.22 +/- 0.15, 0.93 +/- 0.09, 0.66 +/- 0.09, P < 0.0001) was still observed, with patients in the III and IV quartite showing a blunted response compared with controls (1.44 +/- 0.08). Both in diabetics and controls, the ACh/SNP ratio was reciprocally related to Hct (r = -0.46 and r = -0.66, respectively, P < 0.002 for both). This association was independent of comorbidities, gender, metabolic control, plasma lipids, or concomitant treatments, was stronger in the subjects with preserved endotheliumdependent dilatation, and was unchanged when haemoglobin replaced Hct. Conclusion Both in diabetics and non-diabetics, haematocrit is inversely related to small vessel endothelium-dependent dilatation. Thus, in addition to blood rheology, a direct negative effect on nitric oxide availability might explain the link between high Hct and cardiovascular disease.