Endothelin-1 Inhibits Nitric Oxide Synthesis in Vascular Smooth Muscle Cells
作者:
Uichi Ikeda,
Keiji Yamamoto,
Yoshikazu Maeda,
Masahisa Shimpo,
Toshiko Kanbe,
Kazuyuki Shimada,
期刊:
Hypertension
(OVID Available online 1997)
卷期:
Volume 29,
issue 1
页码: 65-69
ISSN:0194-911X
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
We investigated the effects of endothelin-1 on nitric oxide synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of nitric oxide, and the expression of inducible nitric oxide synthase mRNA and protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1beta (10 ng/mL) for 24 hours caused a significant increase in nitrite production. Endothelin-1 significantly decreased the interleukin-1beta-induced nitrite production by vascular smooth muscle cells in a dose-dependent manner (10-11to 10-8mol/L). Incubation with interleukin-1beta for 24 hours induced expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells, whereas endothelin-1 showed a suppressive effect on their expressions. Addition of the endothelin type A receptor antagonist BQ-485, but not the endothelin type B receptor antagonist BQ-788, dose-dependently inhibited the effect of endothelin-1. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 hours, the effect of endothelin-1 was abolished. These results indicate that endothelin-1 acts on endothelin type A receptors and inhibits nitric oxide synthesis in interleukin-1beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway. (Hypertension. 1997;29:65-69.)
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