Vasoconstriction to endothelin-1 is blunted in non-insulin-dependent diabetes: A dose-response study

The haemodynamic hypothesis for the pathogenesis of diabetic microangiopath y argues that an initial increase in microvascular blood flow leads to micr ovascular sclerosis and disturbed autoregulation. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide that contributes to basal vasc ular tone. Impairment of the vasoconstrictor response to ET-1 could result in hyperperfusion anti subsequent microvascular damage. The purpose of this study was to determine whether vascular responses to ET-1 are impaired in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes). Te n patients with type 2 diabetes and nine control subjects underwent brachia l artery cannulation. Forearm blood flow was measured using strain-gauge ve nous occlusion plethysmography. ET-1 in three doses of 5, 10, and 20 pmol/m in and 0.9% saline placebo was infused in a balanced double-blind randomise d manner. Vascular smooth muscle function also was assessed using sodium ni troprusside. Control subjects showed vasoconstriction to ET-1 of 5 (p < 0.0 5), 10 (p < 0.05), and 20 pmol/min (p < 0.01). In the diabetic group, there was no significant response to ET-1 at 5 pmol/min (p > 0.05), however, sig nificant vasoconstriction developed at 10 and 20 pmol/min (p < 0.01). There was a significant difference in response to ET-1 at 5 pmol/min between the diabetic and control groups (p < 0.05). Responses to sodium nitroprusside were similar in both groups (p > 0.05). Patients with type 2 diabetes have a blunted vasoconstrictor response to ET-1 despite preserved vascular smoot h muscle function.