Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor β1 null mouse

Transforming growth factor β1 null mice (TGF-β1(-/-)) suffer from multifocal inflammation and die by 3-4 wk of age. In these mice, levels of nitric oxide (NO) reaction products in serum are elevated approximately fourfold over levels m controls, peaking at 15-17 d of life. Short-term treatment of TGF-β1(-/-) mice with N(G)-monomethyl-L-arginine suppressed this elevated production of NO. Expression of inducible NO synthase (iNOS) mRNA and protein is increased in the kidney and heart of TGF-β1(-/-) mice. These findings demonstrate that TGF-β1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-β1 in vitro.