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Angiotensin II inhibits interleukin-1 beta-induced nitric oxide production in cultured rat mesangial cells.

Research paper by M M Kihara, M M Yabana, Y Y Toya, S S Kobayashi, T T Fujita, T T Iwamoto, T T Ishigami, S S Umemura

Indexed on: 14 Apr '99Published on: 14 Apr '99Published in: Kidney International



Abstract

Macrophage-type nitric oxide synthase (NOS-II) is expressed in glomerular mesangial cells in response to inflammatory cytokines. Nitric oxide (NO) has antithrombotic and cytostatic activities in glomerular diseases. Recent studies have suggested that several vasoactive substances and growth factors modulate NO production in a tissue-specific manner. The aim of this study was to examine whether angiotensin II and transforming growth factor-beta (TGF-beta) modulate cytokine-stimulated NO production and NOS-II gene expression in rat glomerular mesangial cells.Cultured rat mesangial cells were incubated with interleukin-1 beta (IL-1 beta) for 24 hours. The effects of angiotensin II and TGF-beta on stimulated nitrite accumulation and NOS-II mRNA levels were determined.Angiotensin II and TGF-beta significantly decreased IL-1 beta-stimulated nitrite accumulation. The angiotensin type 1 receptor antagonist CV11974 prevented angiotensin II-mediated inhibition of NO production. TGF-beta-neutralizing antibody reversed the effect of TGF-beta without affecting angiotensin II-mediated inhibition of NO production. TGF-beta markedly decreased steady-state levels of NOS-II mRNA and the half-life of the message, whereas angiotensin II did not alter these parameters.These results suggest that in mesangial cells, angiotensin II and TGF-beta participate in the inhibitory regulation of cytokine-induced NO production. TGF-beta inhibits NO production by decreasing NOS-II mRNA levels, whereas angiotensin II may regulate NO production at the levels after NOS-II gene expression. An autocrine action of TGF-beta induced by angiotensin II is unlikely to contribute to angiotensin II-mediated inhibition of NO production.