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.
|Autori:||Natali A; Toschi E; Baldeweg S; Casolaro A; Baldi S; Sironi AM; Yudkin JS; Ferrannini E|
|Titolo:||Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels RID C-1988-2008|
|Anno del prodotto:||2005|
|Digital Object Identifier (DOI):||10.1093/eurheartj/ehi113|
|Appare nelle tipologie:||1.1 Articolo in rivista|