In two double-blind, placebo controlled studies, we tested the effects of intranasal administration of 500 micrograms of a competitive kinin receptor antagonist, [DArg0, Hyp3, DPhe7]-bradykinin (NPC 567), on the response to nasal provocation with 20 micrograms of bradykinin. Nasal lavage was performed before and after provocation, and subjects recorded symptom scores. Lavages were assayed for albumin and TAME-esterase activity (indicators of vascular permeability). 2. In our initial study, 12 subjects received NPC 567 or placebo 5 min before bradykinin. After placebo, bradykinin challenge resulted in values (mean +/- s.e. mean) for albumin, TAME-esterase activity and total symptom scores of 275 +/- 51 micrograms ml-1, 32.1 +/- 7.2 counts min-1 x 10(-3), and 1.8 +/- 0.5, respectively. After NPC 567, bradykinin challenge resulted in values of 317 +/- 99 micrograms ml-1, 31.4 +/- 6.9 counts min-1 x 10(-3), and 2.6 +/- 0.4 for these parameters. No significant difference was observed between placebo and drug treatment for any parameter. 3. To evaluate if the lack of drug effect was due to its enzymatic degradation prior to bradykinin administration, a second study was performed in which NPC 567 was coadministered with bradykinin (n = 8). After placebo-bradykinin challenge, values of 168 +/- 42 micrograms ml-1, 11.3 +/- 4.0 counts min-1 x 10(-3), and 2.8 +/- 0.6 were recorded for albumin, TAME-esterase activity, and symptom scores, respectively, while following NPC 567-bradykinin challenge, these values were 174 +/- 51 micrograms ml-1, 12.3 +/- 4.1 counts min-1 x 10(-3), and 3.1 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)
