Diminished nitric oxide production following administration of transforming growth factor-β1 using a noninflammatory wound repair model

The effects of transforming growth factor-beta 1 (TGF-beta 1) on systemic nitric oxide (NO) production and wound repair were evaluated using a noninflammatory mouse perforated mesentery connective tissue repair model. Urinary nitrates were monitored as a measure of NO production. TGF-beta 1 [bovine serum albumin (BSA) carrier and TGF-beta 1 BSA carrier free] were administered on days 0 and 1 and were evaluated in mice over a 10-day period. A significant decrease in the average postwounding urinary nitrate levels compared to prewounding levels was observed within the TGF-beta 1 treatment group animals (P less than or equal to 0.001) with an insignificant change for the phosphate-buffered saline control animals (P less than or equal to 0.10). Additionally, TGF-beta 1-treated animals showed significant connective tissue repair compared to controls without a concurrent; increase in postwounding urinary nitrate levels, supporting the noninflammatory nature of the perforated mesentery model. Our findings suggest that an unforseen consequence of TGF-beta 1 administration is diminished basal nitric oxide production. When using TGF-beta 1 in a wound repair or other therapeutic model, the administration of an exogenous NO donor compound may be necessary in order to ensure homeostasis, thereby avoiding undesired physiological consequences due to diminished basal NO production. (C) 1999 Academic Press.