Effect of NO-synthase and arginase inhibition in airway hyperreactivity.
BACKGROUND
The decreased L-arginine bioavailability, the basic substrate for nitric oxide synthesis, can be one of the factors contributing to the airways hyperreactivity.


OBJECTIVE
We investigated the effect of various inhibitors of the enzyme activities utilizing L-arginine in a guinea pig model of experimental ovalbumin-induced airway hyperreactivity.


METHODS
We used the in vivo pre-treatment with non-specific inhibitor of NO synthase No-nitro-L-arginine metylester (L-NAME) and relatively specific inhibitor of inducible NO synthase--aminoguanidine. Inhibitors were administered in one-shot (on the 14th day, 30 minutes before the inhalation of ovalbumin) or in a long-time regime (during the whole period of sensibilization by ovalbumin--14 days). We administered the inhibitor of arginase Nomega-hydroxy-L-arginine (NOHA) to the tracheal and lung tissue smooth muscle strips from sensibilized animals.


RESULTS
We observed an increase in the tracheal smooth muscle response to histamine in animals that received an inhalation dose of L-NAME (40 mg/kg b.w.) or aminoguanidine (50 mg/kg b.w.) 30 minutes before the inhalation of ovalbumin but did not evoke any significant difference in the reactivity of lung tissue smooth muscle. Tracheal smooth muscle responded with enhanced contraction amplitude to histamine after chronic pre-treatment with L-NAME or aminoguanidine. The inhibition of arginase with NOHA in vitro decreased the tracheal and lung tissue smooth muscle reactivity to histamine.


CONCLUSIONS
The results suggest that NO-synthase isoforms as well as arginase are involved in the production of NO and in the control of bronchomotoric tonus (Fig. 4, Tab. 2, Ref. 31). Full Text (Free, PDF) www.bmj.sk.
Strapkova
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Department of Pharmacology, Comenius University, Jessenius Faculty of Medicine, Martin, Slovakia. astrapkova@jfmed.uniba.sk
Antosova
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Nosalova
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D000485:Allergens; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000485:Allergens; D004791:Enzyme Inhibitors; D006146:Guanidines; C068309:N(omega)-hydroxyarginine; D010047:Ovalbumin; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; D001119:Arginase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester