Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Natali
Andrea
A
Department of Internal Medicine, Via Roma 67, 56100 Pisa, Italy. anatali@ifc.cnr.it
Toschi
Elena
E
Baldeweg
Stephanie
S
Casolaro
Arturo
A
Baldi
Simona
S
Sironi
Anna Maria
AM
Yudkin
John S
JS
Ferrannini
Ele
E
D000109:Acetylcholine / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006400:Hematocrit; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D009599:Nitroprusside; D008687:Metformin; D000109:Acetylcholine