Arginase and Arginine Dysregulation in Asthma

Table 2

Altered nitric oxide metabolism in allergic asthma.

	Stage of allergic asthma*
	EAR	LAR	AHR	Inflammation	Remodeling
NO	↓	↑	↑	↑	↓?
cNOS	↓	↔	↔	↔	?
iNOS	↔	↑	↑	↑	?
Arginase	↑	↑	↑	?	↑?

*Production of nitric oxide (NO) during different stages of asthma is related to the balance of NOS (nitric oxide synthase) and arginase activity. During the early asthmatic reaction (EAR), increased arginase activity leads to deficiency of L-arginine substrate for cNOS (constitutive NOS), thereby decreasing NO production. iNOS (inducible NOS) is upregulated during the late asthmatic reaction (LAR) leading to increased NO production, at the same time as arginase activity increases, and airway hyperresponsiveness (AHR) increases. The availability of L-arginine substrate for both NOS and arginase may drive reactions and can contribute to proinflammatory peroxynitrite formation under low L-arginine conditions. Elevated NO and iNOS are clearly associated with chronic allergic inflammation, but the role of arginase in this stage is less apparent. At this time, little is known about the roles of NO, NOS, and arginase during airway remodeling in asthma, and further studies are needed to elucidate these pathways.