Natali Andrea, Toschi Elena, Baldeweg Stephanie, Casolaro Arturo, Baldi Simona, Sironi Anna Maria, Yudkin John S, Ferrannini Ele
Department of Internal Medicine, Via Roma 67, 56100 Pisa, Italy.
Eur Heart J. 2005 Mar;26(5):464-71. doi: 10.1093/eurheartj/ehi113. Epub 2005 Feb 3.
In conditions such as type 2 diabetes, hypertension, and smoking, in which haematocrit (Hct) tends to be higher, endothelial function is impaired. In vitro, haemoglobin neutralizes nitric oxide very effectively. Whether red blood cells participate in the regulation of endothelial function in vivo has not been established.
Clinical and haematological 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 dose-response curves to both SNP and ACh. In diabetics, across quartiles of Hct, ACh blood flow responses were progressively lower (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, glycated haemoglobin (HbA(1c)), blood pressure, serum total and HDL-cholesterol 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 quartiles (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 quartile 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 endothelium-dependent dilatation, and was unchanged when haemoglobin replaced Hct.
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.
在2型糖尿病、高血压和吸烟等情况下,血细胞比容(Hct)往往较高,内皮功能会受到损害。在体外,血红蛋白能非常有效地中和一氧化氮。红细胞是否在体内参与内皮功能的调节尚未明确。
对84例2型糖尿病患者和19例对照者测量了临床和血液学参数以及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ACh的剂量反应曲线均变钝。在糖尿病患者中,按Hct四分位数划分,ACh血流反应逐渐降低(881±96、652±81、513±54、307±46%,P<0.0001),尽管年龄、体重指数、糖化血红蛋白(HbA1c)、血压、血清总胆固醇和高密度脂蛋白胆固醇水平、胰岛素敏感性指数及炎症标志物相似,但最大SNP反应也趋于降低(706±72、578±61、607±69、499±53%,P=0.06)。将ACh反应按SNP反应进行标准化(ACh/SNP比值)后,仍观察到Hct四分位数间的逐渐降低(1.54±0.23、1.22±0.15、0.93±0.09、0.66±0.09,P<0.0001),与对照组相比,处于第三和第四四分位数的患者反应变钝(1.44±0.08)。在糖尿病患者和对照组中,ACh/SNP比值均与Hct呈负相关(分别为r=-0.46和r=-0.66,两者P<0.002)。这种关联独立于合并症、性别、代谢控制、血脂或同时进行的治疗,在具有保留的内皮依赖性扩张的受试者中更强,当用血红蛋白替代Hct时无变化。
在糖尿病患者和非糖尿病患者中,血细胞比容均与小血管内皮依赖性扩张呈负相关。因此,除血液流变学外,对一氧化氮可用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。