Selective enhancement of sensitivity to endothelin-1 despite normal endothelium-dependent relaxation in subcutaneous resistance arteries isolated from patients with Type I diabetes

Type I diabetes mellitus is associated with abnormal vascular function, but few studies have documented its effects on human resistance arteries. This study aimed to determine whether endothelial cell and smooth muscle cell function was impaired in resistance arteries isolated from patients with this condition. Biopsies of subcutaneous gluteal fat were taken from 12 patients with Type I diabetes (age 32.3±1.9 years; duration of diabetes 13.9±2.5 years) and 12 matched controls (age 31.5±2.2 years). Levels of glycosylated haemoglobin were higher (P < 0.0001) in patients (9.38±0.35%) than in controls (5.48±0.11%), but most (11 out of 12) patients showed no evidence of microvascular disease. Small resistance arteries were isolated from the biopsies, and isometric responses to vasoconstrictors and vasodilators were measured in a small-vessel myograph. The magnitude and sensitivity of responses to noradrenaline and potassium were not different in diabetic patients compared with controls. In contrast, the sensitivity (pD₂; negative logarithm of the concentration of the vasoconstrictor required to produce 50% of the maximum effect), but not the magnitude, of contraction in response to endothelin-1 in vessels from patients (8.87±0.12) was significantly (P = 0.02) greater than in those from controls (8.40±0.13). Endothelium-dependent (acetylcholine, bradykinin, A23187) and -independent (3´-morpholinosydnonimine) relaxation responses were unaltered in patients with Type I diabetes. These results suggest a selective alteration in receptor activity in the endothelium, and contrast strikingly with the considerable evidence of impaired endothelium-dependent relaxation in Type I diabetes. The present study indicates, therefore, that endothelial cell function is largely maintained in resistance arteries from patients with well controlled Type I diabetes. The increased response to endothelin-1 supports the possibility that more significant abnormalities would be evident in patients with severe microvascular complications.