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Selective blockade of the endothelin subtype A receptor decreases early atherosclerosis in hamsters fed cholesterol.
Kowala, M C; Rose, P M; Stein, P D; Goller, N; Recce, R; Beyer, S; Valentine, M; Barton, D; Durham, S K.
Afiliación
  • Kowala MC; Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Am J Pathol ; 146(4): 819-26, 1995 Apr.
Article en En | MEDLINE | ID: mdl-7717449
Recent studies suggest that endothelin and its receptors may be involved in atherogenesis. To test this hypothesis, cholesterol-fed hamsters were treated with a selective endothelin subtype A (ETA) receptor antagonist BMS-182874. Characterization of hamster atherosclerotic plaques indicated that they contained a fibrous cap of smooth muscle cells, large macrophage-foam cells, and epitopes of oxidized low density lipoprotein. Messenger RNA for both ETA and ETB receptors was detected in aortic endothelial cells, in medial smooth muscle cells, and in macrophage-foam cells and smooth muscle cells of the fibro-fatty plaques. BMS-182874 inhibited the endothelin-1-induced pressor response whereas the depressor effect was unaltered, suggesting that vascular ETA receptors were selectively blocked in vivo. In hyperlipidemic hamsters, BMS-182874 decreased the area of the fatty streak by reducing the number and size of macrophage-foam cells. The results indicated that ETA receptors and thus endothelin promoted the early inflammatory phase of atherosclerosis.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteriosclerosis / Compuestos de Dansilo / Antagonistas de los Receptores de Endotelina Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Am J Pathol Año: 1995 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arteriosclerosis / Compuestos de Dansilo / Antagonistas de los Receptores de Endotelina Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Am J Pathol Año: 1995 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos