ROLE OF NEUTRAL ENDOPEPTIDASE AND KININASE-II ON SUBSTANCE-P-INDUCED INCREASE IN NASAL OBSTRUCTION IN PATIENTS WITH ALLERGIC RHINITIS

We studied the role of neutral endopeptidase (NEP) and kininase II (an giotensin-converting enzyme; ACE) in the modulation of exogenous subst ance P (SP)-induced nasal response in normal subjects and in patients with allergic rhinitis. We measured the nasal conductance in response to increasing doses of SP 2 h after oral administration of either plac ebo or the ACE inhibitor, cilazapril (5 mg), or the NEP inhibitor, ace torphan (300 mg), given in a randomized, double-blind, cross-over mann er. We performed three separate studies: acetorphan versus placebo and cilazapril versus placebo, in normal subjects (n = 6 and n = 8, respe ctively), and acetorphan versus cilazapril versus placebo in patients with allergic rhinitis (n = 6). In normal as well as in rhinitic subje cts, SP decreased nasal conductance in a dose-dependent fashion (p < 0 .001). With placebo, the decrease in nasal conductance in normal subje cts was similar to that in patients with allergic rhinitis (p > 0.5). In normal subjects, acetorphan potentiated the decrease in nasal condu ctance (p < 0.001), whereas cilazapril did not (p = 0.12). In patients with allergic rhinitis, the decrease in nasal conductance was potenti ated by acetorphan (p < 0.001) and by cilazapril (p < 0.001). With ace torphan, the decrease in nasal conductance was not different in patien ts with allergic rhinitis and in normal subjects (p > 0.9). Conversely , with cilazapril, the nasal response to SP was greater in patients wi th allergic rhinitis than in normal subjects (p < 0.001). We conclude that NEP is present in nasal mucosa and modulates SP-induced nasal res ponse in a similar manner in normal subjects and in patients with alle rgic rhinitis. ACE is not involved in the SP-induced nasal response in normal subjects. However, in patients with allergic rhinitis, besides NEP, ACE appears implicated in the degradation of SP.