Induction by inhibitors of nitric oxide synthase of hyperresponsiveness inthe human nasal airway

I The effects of inhibitors of nitric oxide synthase (NOS) on the responsiv eness of the human nasal airway were investigated, by measuring the nasal r esponse to histamine and bradykinin. 2 Repeated intranasal administration of N-G-nitro-L-arginine methyl ester ( L-NAME) or N-G-monomethyl-L-arginine (L-NMMA), 1 mu mol per nostril every 3 0 min for 6 h, increased the nasal obstruction induced by histamine, 50-500 mu g, and bradykinin, 200 mu g per nostril. A single administration of L-N AME, I mu mol per nostril did not induce hyperresponsiveness to histamine. 3 Pretreatment with L-arginine, 30 mu mol, abolished the hyperresponsivenes s to histamine caused by L-NAME, 1 mu mol. Pretreatment with NG-nitro-D-arg inine methyl ester (D-NAME), 1 mu mol, did not induce hyperresponsiveness t o histamine. 4 Repeated administration of L-NAME, I mu mol, caused a significant reducti on in the amount of nitric oxide measured in the nasal cavity. 5 Neither L-NMMA, 1 mu mol, nor L-arginine, 30 mu mol, altered the nasal hy perresponsiveness induced by platelet activating factor (PAF), 60 mu g. PAF did not alter the levels of nitric oxide in the nasal cavity. 6 The results suggest that inhibition of nitric oxide synthase induces a hy perresponsiveness in the human nasal airway, and that this occurs by a mech anism different from that involved in PAF-induced hyperresponsiveness.