on September 9, 2002
Published online before print September 9, 2002, doi: 10.1161/01.CIR.0000032260.01569.64
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Submitted on May 20, 2002
From the Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. Dr Cardillo is presently at Università Cattolica del Sacro Cuore, Rome, Italy. * To whom correspondence should be addressed. E-mail: julio.a.panza{at}medstar.net.
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 ETA 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 ETB 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 ETA 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 ETA 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.
Revised on July 23, 2002
Accepted on July 23, 2002
Increased Activity of Endogenous Endothelin in Patients With Type II Diabetes Mellitus
Carmine Cardillo MD,
Key words: endothelin • diabetes • vasculature • receptors • atherosclerosis
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