Increased activity of endogenous endothelin in patients with type II diabetes mellitus.
Circulation
; 106(14): 1783-7, 2002 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-12356630
ABSTRACT
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 ANDRESULTS:
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Endotelinas
/
Diabetes Mellitus Tipo 2
Tipo de estudio:
Clinical_trials
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circulation
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos