Nasal effects of bradykinin and capsaicin: influence on plasma protein leakage and role of sensory neurons.
Nasal insufflation with bradykinin induces nasal discomfort, rhinorrhea, and nasal blockage, all features of rhinitis. We recently showed these effects to be mediated by the B2-receptor subtype, which has been identified at neural and vascular sites. To investigate the relative contribution of capsaicin-sensitive sensory neural stimulation to the action(s) of bradykinin, two randomized double-blind placebo-controlled studies have been undertaken comparing the nasal effects of single-dose administrations of bradykinin (1.88 x 10(-3) M) and capsaicin (3.28 x 10(-5) M). In comparison with placebo, both bradykinin and capsaicin induced nasal pain/discomfort (P less than 0.01) and rhinorrhea (P less than 0.02). Bradykinin significantly increased nasal airways resistance (P less than 0.005) and plasma protein exudation (P less than 0.02). No such changes were identified after nasal challenge with capsaicin. These findings suggest that bradykinin-induced nasal discomfort and rhinorrhea are neurally mediated, whereas the effects on nasal airways resistance and plasma protein exudation are due to a direct vascular action. In addition, these findings question the role of capsaicin-sensitive sensory neurons in nasal vasculature responses, because no vascular effects of capsaicin could be identified in the human nasal mucosa.
Rajakulasingam
K
K
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
Polosa
R
R
Lau
L C
LC
Church
M K
MK
Holgate
S T
ST
Howarth
P H
PH
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000139:chemically induced; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology
D001798:Blood Proteins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D002211:Capsaicin; D001920:Bradykinin