IMPAIRED VASOCONSTRICTION TO ENDOTHELIN-1 IN PATIENTS WITH NIDDM

Microvascular disease is an important cause of morbidity in diabetes. There is evidence that impaired autoregulation of blood flow is involv ed in the pathogenesis of diabetic microangiopathy. The vascular endot helium plays a central role in the regulation of vascular tone. Endoth elin (ET)-1 is a potent endothelium-derived vaso-constrictor substance that contributes to basal vascular tone. Impaired vasoconstriction in response to endogenous ET could result in hyperperfusion and subseque nt microvascular damage. The purpose of our study was to determine whe ther vascular responses to locally administered ET-1 are impaired in N IDDM. Nine patients with NIDDM and 12 control subjects underwent cannu lation of the nondominant brachial artery, Forearm blood flow (FBF) wa s measured at baseline and during the drug infusion using strain-gauge venous occlusion plethysmography. ET-1 (5 pmol/min) was infused for 6 0 min at a rate of 1 ml/min. FBF was measured during the first 5 min o f the infusion and at 5-min intervals thereafter, Results were express ed as change in FBF from baseline (ml . 100 ml(-1) min(-1)) and were a nalyzed using repeated measures analysis of variance and Dunnett's tes t of multiple comparisons. Control subjects showed a gradual onset of vasoconstriction in response. to ET-I, which reached maximum at 35 min (1.1 ml . 100 ml(-1). min(-1);P < 0.01). There was no reduction in FBF in response to ET-1 in the diabetic group, The differences between th e diabetic and control groups were significant (P < 0.03). In conclusi on, ET-1 infused locally at 5 pmol/min does not cause vasoconstriction in patients with NIDDM.