ICAM-1 EXPRESSION ON CARDIAC MYOCYTES AND AORTIC ENDOTHELIAL-CELLS VIA THEIR SPECIFIC ENDOTHELIN RECEPTOR SUBTYPE

Endothelin-1 (ET-1) and Endothelin-3 (ET-3) increased the expression o f intercellular adhesion molecule-1 (ICAM-1) on rat neonatal cultured cardiac myocytes and rat aortic endothelial cells. ET-1-induced ICAM-1 expression on cardiac myocytes was inhibited by a selective ET(A) rec eptor antagonist, S-0139, but not by a selective ET(B) receptor antago nist, BQ788. ET-3-induced ICAM-1 expression on endothelial cells was i nhibited by BQ788 but not by S-0139. Protein kinase C (PKC) inhibitor staurosporine inhibited ETs-induced ICAM-1 expression on both cell typ es. Treatment of the cells with ETs increased neutrophil adhesion, whi ch was inhibited by S-0139 and staurosporine on cardiac myocytes and b y BQ788 and staurosporine on endothelial cells. These results suggest that ETs induce neutrophil adhesion to cardiac myocytes and aortic end othelial cells by increasing ICAM-1 expression, which mediate via ET(A ) receptor on cardiac myocytes and via ET(B) receptor on aortic endoth elial cells. ICAM-1 expression induced by activation of ET(A) and ET(B ) receptors appears to be mediated through the PKC pathway. (C) 1996 A cademic Press