75 Gen. Physiol. Biophys. (2011), 30, 75–83 doi:10.4149/gpb_2011_01_75 Competition of NO synthases and arginase in the airways hyperreactivity Anna Strapkova and Martina Antosova Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia Abstract. Te competition between arginases and NO synthases (NOS) for their common substrate L-arginine can be important in the airways hyperreactivity. We investigated the effect of the simul- taneous modulation of arginase and NOS activities in allergen-induced airways hyperreactivity. We analysed the response of tracheal and lung tissue smooth muscle to histamine or acetylcholine afer administration N ω -nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and N ω -hydroxy-L-arginine (NOHA) in the combinations in in vitro conditions. Te results show the decrease of ovalbumin-induced hyperreactivity afer inhibition of arginase activity with NOHA. A supplementation of L-arginine caused favourable effect on the airway smooth muscle response. We found the airway reactivity decrease on the whole if we used the combination of NOS and ar- ginase inhibitors. Te inhibition of both types of enzymes caused more expressive effect in tracheal smooth muscles. We recorded the difference in the response to histamine or acetylcholine. Te simultaneous inhibition of iNOS (with AG) and arginase (with NOHA) evoked the most expressive effect. Results show the importance of competition of both types enzymes – NOS and arginase for the balance of theirs activities in the control of airways bronchomotoric tone in the conditions of the airways hyperreactivity. Key words: Airway hyperreactivity — Ovalbumin — Guinea pig — Arginase — NOS Abbreviations: AG, aminoguanidine; cGMP, cyclic GMP; eNOS, endothelial NOS; NOS, NO syn- thase; L-NAME, N ω -nitro-L-arginine methyl ester; nNOS, neuronal NOS; NOHA, N ω -hydroxy-L- arginine. Correspondence to: Anna Strapkova, Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Sklabinská 26, 037 53 Martin, Slovakia E-mail: astrapkova@jfmed.uniba.sk Introduction Some of the airway diseases (asthma, chronic obstructive pulmonary disease) are characterized by the airway inflam- mation and airway hyperresponsiveness. Te prevalence of these diseases is increasing on regardless of new therapeutic approaches (Stirling and Chung 2000). New insights into the pathophysiology of airway diseases could lead to addi- tional effective therapeutic approaches for their treatment (Ten Broeke et al. 2004). Nitric oxide (NO) might be one of “new” targets, as an extraordinary important bio messenger for a number of inter- and intracellular signalling pathways, including function of respiratory system (Redington 2006). Here, NO causes bronchodilation, vasodilation, it partici- pates in the regulation of gas exchange, blood flow, mucocili- ary transport, surfactant production and also represents an important non-specific defence mechanism in the airways. Nitric oxide is produced by family of enzymes NO syn- thase (NOS) isoforms that utilize the semi-essential amino acid L-arginine as a substrate for the NO and L-citrulline production (Moncada et al. 1989). In the airways the con- stitutive NOS (cNOS) isoforms are mainly expressed in the neurons of inhibitory nonadrenergic noncholinergic (iN- ANC) nervous system (nNOS), in the endothelium (eNOS) and in the epithelium (nNOS and eNOS), whereas inducible NOS (iNOS) induced by proinflammatory cytokines during airway inflammation is expressed mainly in macrophages and epithelial cells (Ricciardolo 2003).