Intraarterial infusion of BQ-123 caused significant vasodilation in patients with type II diabetes (P<0.001) but not in healthy controls, indicating enhanced endogenous ET-1 activity.
Case-Control (n=27)
Does endogenous ET-1 activity differ in the resistance vessels of patients with type II diabetes mellitus compared to healthy controls?
Patients with type II diabetes exhibit enhanced endogenous ET-1 activity on ET(A) receptors and blunted sensitivity to exogenous ET-1, suggesting a mechanism for diabetic vascular complications.
p-value: p=<0.001
BACKGROUND: Endothelial dysfunction may contribute to the risk of premature atherosclerosis in patients with diabetes. Endothelin (ET-1) may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion. We sought to assess the activity of endogenous ET-1 in a group of patients with type II diabetes mellitus with the use of antagonists of ET-1 receptors. METHODS AND RESULTS: Forearm blood flow (FBF) responses (strain gauge plethysmography) to intraarterial infusion of a selective blocker of ET(A) receptors (BQ-123) and, on a different occasion, to ET-1, were measured in 15 patients with diabetes and 12 healthy controls. In addition, 5 patients with diabetes received coinfusion of BQ-123 and BQ-788 (a selective blocker of ET(B) receptors). In normal subjects, BQ-123 did not significantly modify FBF from baseline (P=0.16). In contrast, BQ-123 administration resulted in a significant vasodilator response in patients with diabetes (P<0.001). Infusion of exogenous ET-1 resulted in lower vasoconstrictor responses in patients with diabetes than in controls (P=0.001), whereas the vasoconstrictor response to norepinephrine was similar in the 2 groups (P=0.78). In patients with diabetes, the vasodilator response to selective ET(A) blockade was not significantly modified by nonselective blockade of ET-1 receptors obtained by coinfusion of BQ-123 and BQ-788. CONCLUSIONS: The activity of endogenous ET-1 on ET(A) receptors is enhanced in the resistance vessels of patients with diabetes, whereas their sensitivity to exogenous ET-1 is blunted. This abnormality may participate in the pathophysiology of vascular complications associated with diabetes.
Cardillo et al. (Mon,) conducted a case-control in Type II diabetes mellitus (n=27). Intraarterial infusion of BQ-123 and ET-1 vs. Healthy controls was evaluated on Forearm blood flow (FBF) response to intraarterial infusion of BQ-123 (p=<0.001). Intraarterial infusion of BQ-123 caused significant vasodilation in patients with type II diabetes (P<0.001) but not in healthy controls, indicating enhanced endogenous ET-1 activity.