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.
Saturday, October 25, 2008
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Nice to find more evidence to support the anti-inflammatory diet :)
Br J Nutr. 2011 Aug;106(3):441-50.
Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control.
Barros R, Moreira A, Fonseca J, Delgado L, Castel-Branco MG, Haahtela T, Lopes C, Moreira P.
Source
Faculty of Nutrition and Food Sciences, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal. renatabarros@fcna.up.pt
Abstract
As recently described, adherence to the Mediterranean diet is associated with improved asthma control. However, evidence of how specific nutrients such as fatty acids and antioxidants may affect this relationship remains largely unknown. We aimed to examine the association between dietary intake of fatty acids and antioxidants and asthma control. A cross-sectional study was developed in 174 asthmatics, mean age of 40 (SD 15) years. Dietary intake was obtained by a FFQ, and nutritional content was calculated using Food Processor Plus™ software (ESHA Research, Inc., Salem, OR, USA). Good asthma control was defined by the combination of forced expiratory volume during the first second, exhaled NO (eNO) and Asthma Control Questionnaire (ACQ) score (control: forced expiratory volume in the first second ≥80 %; eNO ≤35 ppb; ACQ <1·0, scale 0-6 score). Multiple linear and logistic regression models were performed to analyse the associations between nutrients and asthma outcomes, adjusting for confounders. A high n-6:n-3 PUFA ratio predicted high eNO, whereas high intakes of n-3 PUFA, a-linolenic acid (ALA) and SFA were associated with low eNO. Odds for controlled asthma improved along with an increased intake of n-3 PUFA (OR 0·14, 95% CI 0·04, 0·45; P for trend=0·001), SFA (OR 0·36, 95% CI 0·13, 0·97; P for trend=0·047) and ALA (OR 0·18, 95% CI 0·06, 0·58; P for trend=0·005). A high n-6:n-3 PUFA ratio increased the odds for uncontrolled asthma (OR 3·69, 95% CI 1·37, 9·94; P for trend=0·009), after adjusting for energy intake, sex, age, education and use of inhaled corticosteroids. Higher intakes of n-3 PUFA, ALA and SFA were associated with good asthma control, while the risk for uncontrolled asthma increased with a higher n-6:n-3 PUFA ratio. The present results introduce a protective effect of ALA in asthma control, independent of marine n-3 fatty acids, and provide a rationale to dietary intervention studies in asthma.
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