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-length ET-1 [ET-1(1-31)]. In this study we examined effect of ET-1(1-31) on endothelial function. ET-1 (1-31) evoked contraction in a concentration- dependent manner at > 10^-8 M, which was about 10 times weaker than that of conventional ET-1 [ET-1(1-21)]. BQ485, an ETA receptor antagonist, completely abolished ET-1(1-31)-induced contraction, but BQ788, an ETB receptor antagonist, 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 [Ca²⁺]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.