Nitric Oxide Effects on Murine Cardiac Allografts

Abstract

Biosynthesis of nitric oxide (NO) by mammalian cells has recently been demonstrated (Hibbs et al., 1987a; Iyengar et al., 1987; Hibbs et al., 1988; Marietta et al., 1988). NO synthesis is induced during a cell-mediated immune response to infection or tumor development. NO is biologically produced by the enzyme immune/inflammatory NO synthase (iNOS), which utilizes molecular oxygen to oxidatively deiminate a guanidino nitrogen atom of L-arginine with formation of L-citrulline and NO as the products (Hibbs et al., 1988; Marietta et al., 1988, Tayeh et al., 1989). iNOS is competitively inhibited by N-substituted L-arginine derivatives, including N^G -monomethyl-L-arginine (MLA) (Hibbs et al., 1987a, 1987b; Granger et al., 1990, 1991). Nitric oxide reacts with O₂ in a termolecular reaction to produce nitrate (NO₃ ⁻) and nitrite (NO₂ ⁻- NO₂ ⁻ entering the vascular system is further oxidized by hemoglobin to NO₃ ⁻ (Granger et al., 1991) and is excreted in the urine. When exogenous sources of nitrate are eliminated from the diet, urine nitrate can be used as a measure of NO biosynthesis (Granger et al., 1991).