Comparative nasal effects of bradykinin, kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers.
1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists kallidin and bradykinin both induced a dose-dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to kallidin and bradykinin between rhinitic and non-rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis.
Rajakulasingam
K
K
Medicine 1, Centre Block, Southampton General Hospital.
Polosa
R
R
Holgate
S T
ST
Howarth
P H
PH
D000328:Adult; D000403:Airway Resistance / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000502:physiology*; D004311:Double-Blind Method; D006801:Humans; D007609:Kallidin / Q000502:physiology*; D015508:Nasal Obstruction / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000503:physiopathology*; D013329:Structure-Activity Relationship
C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D001920:Bradykinin