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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

ETA receptor mediates altered leukocyte-endothelial cell interaction and adhesion molecules expression in DOCA-salt rats

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Autor(es):
Callera, Glaucia E. ; Montezano, Augusto C. ; Touyz, Rhian M. ; Zorn, Telma M. T. [4] ; Carvalho, Maria Helena C. ; Fortes, Zuleica B. ; Nigro, Dorothy ; Schiffrin, Ernesto L. ; Tostes, Rita C.
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: Hypertension; v. 43, n. 4, p. 872-879, abr. 2004.
Área do conhecimento: Ciências Biológicas - Morfologia
Assunto(s):Histologia   Matriz extracelular   Hipertensão
Resumo

Leukocyte adhesion to endothelial cells plays a key role in inflammatory processes associated with end-organ injury. Endothelin-1 (ET-1), which stimulates inflammatory processes, contributes to cardiovascular damage in deoxycorticosterone (DOCA)-salt hypertension. We investigated whether ETA receptor blockade modulates in vivo leukocyte-endothelial cell interactions and expression of cell adhesion molecules (CAM) involved in these processes. DOCA-salt and control uninephrectomized rats were treated with the ETA antagonist BMS182874 (40 mg/kg per day) or vehicle. Analysis of CAMs expression by reverse transcription-polymerase chain reaction and immunohistochemistry showed increased cardiac platelet selectin (P-selectin), detected mainly in endothelial cells, and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in DOCA-salt rats. Cardiac expression of endothelial selectin (E-selectin) was decreased, whereas immunoreactivity to ED-1 and myeloperoxidase (MPO) activity, markers of macrophage and leukocyte infiltration, respectively, were increased in DOCA-salt. Leukocyte-endothelial cell interaction, functionally assessed in venules of internal spermatic fascia by intravital microscopy, was significantly altered in DOCA-salt rats as evidenced by increased leukocyte adhesion and decreased rolling. BMS182874 treatment normalized leukocyte-endothelium interactions, decreased cardiac VCAM-1 expression in DOCA and control groups, and had no effects on ICAM-1 expression. BMS182874 also increased E-selectin and abolished P-selectin expression in DOCA-salt, but not in control rats. The ETA antagonist reduced cardiac ED-1 content and MPO activity and prevented cardiac damage in DOCA-salt rats. These data indicate that ET-1 participates, via activation of ETA receptors, in altered leukocyte-endothelial cell interactions in DOCA-salt rats, possibly by modulating expression of CAMs, and that the inflammatory status is associated with cardiac damage in mineralocorticoid hypertension. (AU)

Processo FAPESP: 01/13642-3 - Contribuição da endotelina-1 para o estresse oxidativo e processo inflamatório na hipertensão induzida por desoxicorticosterona e salina (DOCA-sal)
Beneficiário:Rita de Cassia Aleixo Tostes Passaglia
Linha de fomento: Auxílio à Pesquisa - Regular