Role of peptidases and NK1 receptors in vascular extravasation induced by bradykinin in rat nasal mucosa.
We used Evans blue dye to assess the effects of bradykinin on vascular extravasation in nasal mucosa of pathogen-free F344 rats. There was a dose-dependent increase in Evans blue extravasation when bradykinin was delivered by topical instillation in the nose (doses, 25-100 nmol). Only the highest intravenous doses (2 and 5 mumol/kg) of bradykinin caused increased extravasation. When bradykinin was delivered by either route, its effect on extravasation was exaggerated by pharmacological inhibition of the enzymes neutral endopeptidase (NEP) and kininase II [angiotensin-converting enzyme (ACE)]. When bradykinin was instilled locally, the effect of NEP inhibition was predominant; when bradykinin was injected intravenously, the effect of ACE inhibition was predominant. The mechanism of extravasation also varied with the mode of bradykinin delivery: when bradykinin was instilled locally in the nose, the selective neurokinin 1 (NK1) receptor antagonist CP-96,345 markedly inhibited the response, whereas it had no effect on Evans blue extravasation when bradykinin was injected intravenously. We conclude that bradykinin causes dose-related increases in Evans blue dye extravasation in the nose and that these effects are exaggerated when NEP and ACE are inhibited. Topically instilled bradykinin causes vascular extravasation to a large extent via NK1 receptor stimulation, thus suggesting a major role for tachykinins released from sensory nerve endings.
Bertrand
C
C
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Geppetti
P
P
Baker
J
J
Petersson
G
G
Piedimonte
G
G
Nadel
J A
JA
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D005070:Evans Blue; D006020:Glycopeptides / Q000494:pharmacology; D006651:Histocytochemistry; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D010447:Peptide Hydrolases / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D001713:Biphenyl Compounds; D006020:Glycopeptides; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D005070:Evans Blue; D002216:Captopril; D010447:Peptide Hydrolases; D015260:Neprilysin; D001920:Bradykinin; C008890:phosphoramidon; C066892:CP 96345