Induction by inhibitors of nitric oxide synthase of hyperresponsiveness in the human nasal airway.
1. The effects of inhibitors of nitric oxide synthase (NOS) on the responsiveness of the human nasal airway were investigated, by measuring the nasal response 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 micromol per nostril every 30 min for 6 h, increased the nasal obstruction induced by histamine, 50 - 500 microg, and bradykinin, 200 microg per nostril. A single administration of L-NAME, 1 micromol per nostril did not induce hyperresponsiveness to histamine. 3. Pretreatment with L-arginine, 30 micromol, abolished the hyperresponsiveness to histamine caused by L-NAME, 1 micromol. Pretreatment with N(G)-nitro-D-arginine methyl ester (D-NAME), 1 micromol, did not induce hyperresponsiveness to histamine. 4. Repeated administration of L-NAME, 1 micromol, caused a significant reduction in the amount of nitric oxide measured in the nasal cavity. 5. Neither L-NMMA, 1 micromol, nor L-arginine, 30 micromol, altered the nasal hyperresponsiveness induced by platelet activating factor (PAF), 60 microg. 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 hyperresponsiveness in the human nasal airway, and that this occurs by a mechanism different from that involved in PAF-induced hyperresponsiveness.
Turner
P J
PJ
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT.
Maggs
J R
JR
Foreman
J C
JC
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D043782:Receptor, Bradykinin B2; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D043782:Receptor, Bradykinin B2; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065679:icatibant; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester