Figure 1 .

Schematic presentation of the role of L-citrulline/L-arginine cycle in the regulation of airway function. The diagram integrates physiologic, biochemical and molecular mechanisms whereby neonatal hyperoxic exposure impairs NO-cGMP signaling and resultant airway smooth muscle relaxation. The L-arginine is a common substrate for NOS and arginase. Hyperoxia increases the lung arginase activity that reduces the bioavailability of L-arginine to NOS. L-citrulline is recycled to L-arginine through ASS and ASL enzymes. It is proposed that L-citrulline competes with NOS blockers (like L-NAME). However, it blocks arginase activity in hyperoxic conditions and thus increases the bioavailibility of L-arginine. The red lines with bars indicate inhibition. ASS, argininosuccinate synthase; ASL, argininosuccinate lyase; CATs, cationic amino acid transporters; cGMP, cyclic guanosine monophosphate; GDP, guanosine diphosphate; GTP, guanosine triphosphate; L-NAME, N^ω-nitro-L-arginine methyl ester; NO, nitric oxide; NOS, nitric oxide synthase; OAT, ornithine amino transferase; ODC, ornithine decarboxylase; PKG, protein kinase G; sGC, soluble guanylate cyclase.