Asthma Nitric Oxide

Arginine is the source of nitric oxide using the enzyme NOS. Inducible NOS is expressed in response to triggers of inflammation mediated by NFkB. NO in turn activates guanylate cyclase to increase cyclic GMP and cGMP relaxes muscle actin and myosin.

Studies are being made to assess the status of asthma by measuring nitric oxide (NO) in respired air. Since NO is produced as a product of the action of induced nitric oxide synthase (iNOS), and iNOS is synthesized when the inflammatory transcription factor NFkB is activated, then the inflammation that is a characteristic of asthma should be signaled by the production of NO.

If NO is involved in asthma, then one would expect relaxation of muscle to occur. That is the opposite of what is observed; contraction of the muscle cells surrounding airways is responsible for airway constriction is asthmatic episodes. Thus, during asthmatic episodes NO must be reduced.

Since NO is made from the amino acid arginine, then the ability to produce NO can be decreased by reducing available arginine. Arginine can be reduced by the enzyme arginase. The product is ornitine that can in turn be converted into purtrescine, the simplest of the polyamines that are used as counterions in the secretion of heparan and chondroitin sulfates.

Arginase is produced in high levels in asthmatics, but not in normal lungs. Also elevated putrescine is found in asthmatic lungs, indicating that arginine is being converted by arginase into ornithine and on to purtrescine. Ornithine is the precursor for proline that is a key amino acid in collagen production and the increased extracellular matrix that thickens the tissue of asthmatic lungs is rich in collagen.

A major point of this discussion is that NO can only be effectively lowered if there is a limited supply of arginine. Thus arginine supplementation should be helpful to asthmatics. Nitroglycerine patches may also be a means of enhancing sources of NO. Another possible approach would be the use of NO donors conjugated to NSAIDS. These conjugates delivered in an atomized form could provide the lungs with both NO and anti-inflammatory agents. Asthmatics also respond well to rigorous application of the anti-inflamatory diet and lifestyle.