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 (angiotensin-converting enzyme; ACE) in the modulation of exogenous substance 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 placebo or the ACE inhibitor, cilazapril (5 mg), or the NEP inhibitor, acetorphan (300 mg), given in a randomized, double-blind, cross-over manner. We performed three separate studies: acetorphan versus placebo and cilazapril versus placebo, in normal subjects (n = 6 and n = 8, respectively), and acetorphan versus cilazapril versus placebo in patients with allergic rhinitis (n = 6). In normal as well as in rhinitic subjects, SP decreased nasal conductance in a dose-dependent fashion (p < 0.001). With placebo, the decrease in nasal conductance in normal subjects was similar to that in patients with allergic rhinitis (p > 0.5). In normal subjects, acetorphan potentiated the decrease in nasal conductance (p < 0.001), whereas cilazapril did not (p = 0.12). In patients with allergic rhinitis, the decrease in nasal conductance was potentiated by acetorphan (p < 0.001) and by cilazapril (p < 0.001). With acetorphan, the decrease in nasal conductance was not different in patients with allergic rhinitis and in normal subjects (p > 0.9). Conversely, with cilazapril, the nasal response to SP was greater in patients with allergic rhinitis than in normal subjects (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Lurie
A
A
Service de Pneumologie and Eclimed, Hôpital Cochin, Université René Descartes, Paris, France.
Nadel
J A
JA
Roisman
G
G
Siney
H
H
Dusser
D J
DJ
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D006801:Humans; D008297:Male; D015508:Nasal Obstruction / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D009299:Nasal Provocation Tests; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D012221:Rhinitis, Allergic, Perennial / Q000150:complications*; D013373:Substance P; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D017315:Cilazapril; D013373:Substance P; C049331:racecadotril; D015244:Thiorphan; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin