Schematic representation of the mechanisms involved in decreased nitric oxide (NO) production in endothelial cells from arthritic rats. Endothelial nitric oxide synthase (eNOS) catalyses the conversion of L-arginine to NO. The upregulation of arginase pathway and the deficit in the co-factor of eNOS tetrahydrobiopterin (BH4) cause uncoupling of eNOS to generate superoxide anions (O2–) which subsequently scavenge NO to generate peroxynitrite (ONOO−). Angiotensin-II (ANG-II) might amplify O2– production by activating NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase after ANG-II type 1 (AT1) receptor activation. Up and down arrows indicate increases or decreases in amount or activity (from [14–23]).