Pharmacology of nasal provocation with bradykinin: studies of tachyphylaxis, cyclooxygenase inhibition, alpha-adrenergic stimulation, and receptor subtype.
We have evaluated mechanisms by which nasal provocation with bradykinin may induce symptoms of rhinitis. Repeated nasal challenges with 100 micrograms of bradykinin led to reproducible increases in symptoms and in vascular permeability. Premedication with aspirin did not alter bradykinin-induced responses. Topical application of the alpha-adrenergic agonist oxymetazoline significantly reduced bradykinin-induced subjective nasal congestion scores, but did not lead to a significant decrease in total symptoms or in vascular permeability. Finally, the B1 kinin receptor agonist des-Arg9-bradykinin (1 mg) was totally ineffective in inducing symptoms or increasing vascular permeability. Thus, nasal provocation with bradykinin leads to induction of symptoms and increased vascular permeability, presumably via stimulation of B2 kinin receptors, and is not dependent on prostanoid generation.
Churchill
L
L
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md.
Pongracic
J A
JA
Reynolds
C J
CJ
Naclerio
R M
RM
Proud
D
D
D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects*; D009299:Nasal Provocation Tests; D010109:Oxymetazoline / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012709:Serum Albumin / Q000032:analysis; D013618:Tachyphylaxis
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D012709:Serum Albumin; C024626:bradykinin, des-Arg(9)-; D010109:Oxymetazoline; D011451:Prostaglandin-Endoperoxide Synthases; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D001241:Aspirin; D001920:Bradykinin