Increased activity of endogenous endothelin in patients with hypercholesterolemia.
J Am Coll Cardiol
; 36(5): 1483-8, 2000 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-11079646
ABSTRACT
OBJECTIVE:
We sought to assess the activity of endogenous endothelin-1 (ET-1) in hypercholesterolemic patients using antagonists of ET-1 receptors.BACKGROUND:
Endothelial dysfunction in hypercholesterolemic patients may contribute to their risk of premature atherosclerosis. Endothelin, a peptide released by endothelial cells, may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion.METHODS:
Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intra-arterial infusion of a selective blocker of ETA receptors (BQ-123) and, on a separate occasion, to ET-1 were measured in 12 hypercholesterolemic patients and 12 normal control subjects. In addition, on a different day, six hypercholesterolemic patients received co-infusion of BQ- 123 and BQ-788 (a selective blocker of ETB receptors).RESULTS:
In normal subjects, BQ-123 did not significantly modify FBF from baseline (p = 0.78); however, in hypercholesterolemic patients, BQ-123 administration resulted in a significant vasodilator response (p < 0.001). Administration of exogenous ET-1 resulted in similar vasoconstrictor responses in patients (37%) and control subjects (35%) (p = 0.83). In hypercholesterolemic patients, the vasodilator response to selective ETA blockade was reversed by nonselective blockade of ET-1 receptors obtained by co-infusion of BQ-123 and BQ-788.CONCLUSIONS:
The vascular activity of endogenous ET-1 is enhanced in hypercholesterolemic patients, whereas their sensitivity to exogenous ET-1 is unchanged. These findings suggest increased production of ET-1, which may participate in the pathophysiology of vascular disease characteristic of hypercholesterolemia.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotelina-1
/
Hipercolesterolemia
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos