Spontaneously increased production of nitric oxide and aberrant expression of the inducible nitric oxide synthase in vivo in the transforming growth factor beta 1 null mouse

Transforming growth factor beta 1 null mice (TGF-beta 1-/-) 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 in controls, peaking at 15-17 d of life. Shortterm treatment of TGF-beta 1-/- mice with NG-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-beta 1-/- mice. These findings demonstrate that TGF-beta 1 negatively regulates iNOS expression in vivo, as had been inferred from mechanistic studies on the control of iNOS expression by TGF-beta 1 in vitro.