Attenuation of human nasal airway responses to bradykinin and histamine by inhibitors of nitric oxide synthase

Abstract

1 The effects of inhibitors of nitric oxide synthase and local anaesthetics were studied on changes in human nasal airway patency and albumin extravasation in response to bradykinin and histamine, in vivo. 2 Compared with the action of the vasoconstrictor, ephedrine, 2.5 ,umol, N0-nitro-L-arginine methyl ester (L-NAME), 1 pmol alone, did not change the resting value of the minimal cross-sectional area (A min) of the human nasal airway. L-NAME, 0.1 to 10 ymol, produced a dose-related inhibition of the reduction in A min caused by bradykinin, 300 pig. NG-monomethyl-L-arginine (L-NMMA), 1 pimol, similarly reduced the effect of bradykinin, 300 ,ug, on A min, but NG-nitro-D-arginine methyl ester (D-NAME), had no effect. L-NAME, 0.1 to 10 pmol, or L-NMMA, 10 imol, failed to inhibit the effect of histamine, 300 pg on A min. 3 The inhibition by L-NAME, 1 ,umol of the action of bradykinin, 300 pg on A min was maximal between 15 and 30 min after pretreatment with L-NAME.4 L-NAME, 1 and 10 pimol, inhibited the extravasation of albumin into the nasal cavity induced by bradykinin, 300 pug, and also by histamine, 300 pug. D-NAME, 1 and 10 ,umol had no effect on the extravasation of albumin in response to bradykinin or histamine. 5 L-Arginine, 30 pmol, reversed the effect of L-NAME, 1 Mmol, on the bradykinin-and histamineinduced albumin extravasation into the nasal airway. 6 Local anaesthesia of the nasal airway with lignocaine, 10 mg, or benzocaine, 10 mg, failed to inhibit the reduction in A min or the albumin extravasation induced by either bradykinin, 300 mig, and histamine, 300 Mig. 7 We conclude that the extravasation of plasma albumin caused by bradykinin and by histamine involves the generation of nitric oxide. The nasal blockage induced by bradykinin involves nitric oxide generation but the nasal blockage induced by histamine does not.

Markedly Increased Nasal Blockage by Intranasal Leukotriene D4 in an Experimental Allergic Rhinitis Model: Contribution of Dilated Mucosal Blood Vessels

“…Based upon the present study's result and a report that L-NAME did not change nasal airway resistance from baseline in healthy subjects (28), NO may not substantially act as a vasodilator in nasal airways under unstimulated conditions.…”

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

“…Histamine exerts its inflammatory effects, in part, through NO generation in situ [35], since the blockade of NOS significantly inhibited histamine-induced plasma extravasation in human nasal airway [42]. Interestingly, Ali and co-workers [43] demonstrated that low concentration of H2S or spontaneous H2S donors reversed histamine, but not isoprenaline-induced vasodilatation, possibly via a direct chemical reaction between H2S and NO, which may lead to the formation of a nitrosothiol [44] or even nitroxyl species (NO-/HNO) [45] of poor vasorelaxant activities.…”

Acetylcholine induces contractile and relaxant effects in canine nasal venous systems

“…To study whether the response to ACh was nitric oxide (NO)-dependent, a cumulative concentration-response curve was determined after the tissue was incubated for 30 min with either: the vehicle; nitro-L-arginine-methyl-ester (L-NAME; an NO synthase (NOS) inhibitor) alone; or L-NAME in combination with L-arginine (a NOS substrate) [11,12]. The concentration of L-NAME (1610 -5 M) used was found to be effective in inhibiting the relaxation induced by calcium ionophore A23187 (1610 -9 -1610 -3 M) in PE-pre-contracted vascular segments.…”