Fig. 6.

Putative mechanisms responsible for the indigo carmine-induced inactivation of endothelial nitric oxide (NO), which may be involved in the indigo carmine-induced enhancement of the contraction evoked by phenylephrine in an isolated rat aorta [7,14,15]. The basal NO is produced by endothelial nitric oxide synthase (eNOS) and NO normally diffuses out of the endothelium to react with guanylyl cyclase (GC), which leads to the production of cyclic guanosine monophosphate (cGMP) and vasorelaxation. Superoxide anion (O₂^·-), which may be produced by enzyme systems (e.g., xanthine oxidase, cyclooxygenase, lipoxygenase, NADPH oxidase, NADPH-cytochrome P450 reductase) stimulated by indigo carmine, inactivates NO to form peroxynitrite (ONOO^-), which leads to the decreased formation of cGMP and the inhibition of vasorelaxation. The decreased formation of cGMP may contribute to the enhanced response to phenylephrine. A low-molecular-weight superoxide anion scavenger, tiron, or superoxide dismutase (SOD) convert O₂^·- to a more stable reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), leading to the inhibition of NO inactivation induced by O₂^·- and the restoration of production of cGMP, which attenuates the augmented response to phenylephrine. (↑): increase, (↓); decrease, GTP: guanosine triphosphate, NADPH: nicotinamide adenine dinucleotide phosphate.