Production of nitric oxide from endothelial cells by 31-amino-acid-length endothelin-1, a novel vasoconstrictive product by human chymase

Human chymase selectively converts big endothelin (ET)-1 to 31-amino-acid-l ength ET-1 [ET-1(1-31)], In this study we examined effect of ET-1(1-31) on endothelial function. ET-L(1-31) evoked contraction in a concentration-depe ndent manner at >10(-8) M, which was about 10 times weaker than that of con ventional ET-1 [ET-1(1-21)]. BQ485, an ETA receptor antagonist, completely abolished ET-1(1-31)-induced contraction, but BQ788, an ETB receptor antago nist, slightly enhanced it, suggesting that ET-1 (1-31) relaxes artery via endothelium. On endothelial cells, ET-1 (1-21) and ET-1 (1-31) increased [C a2+]i and produced NO, both of which were significantly inhibited by BQ788 and not by BQ485, These results indicate that ET-1(1-31) increased [Ca2+]i and produced NO in endothelial cells through ETB receptor similarly with ET -1(1-21), although slight difference in effect on smooth muscle cells, (C) 2000 Elsevier Science Inc. All rights reserved.