The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

Abstract

We have investigated the effects of L-arginine, D-arginine and Llysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, N G -nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a noncompetitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma

“…Since our patients did not have an L-arginine deficient or weighted diet, we cannot exclude the possibility that these subjects had little or no NOS substrate limitation. Finally, since high concentrations of L-arginine have been shown to act as a non-competitive antagonist of the contractile response to histamine in vitro, 6 we cannot exclude the contribution of the anti-histamine eVects of L-arginine to the present findings.…”

“…Previous animal studies have demonstrated the ability of L-arginine to reverse the enhanced bronchoconstriction to non-sensitising stimuli following inhibition of NO synthesis 5 and to reduce contractility to histamine in vitro. 6 In addition, they provided indirect evidence for an association between endogenous NO deficiency and the increase in airway sensitivity and reactivity following either respiratory virus infection 7 or allergen exposure in guinea pigs. 8 Our results do not confirm these findings, although a slight improvement in airway reactivity occurred following supplementation with oral L-arginine.…”