Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways.
T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1-10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2-receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des-Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B2 receptors. The effect is modulated by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.
Yamawaki
I
I
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Takeda
Y
Y
Chiyotani
A
A
Sakai
N
N
Kameyama
S
S
Konno
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects; D010447:Peptide Hydrolases / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D015320:Tachykinins / Q000494:pharmacology
D065168:Bradykinin Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D015320:Tachykinins; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C039065:T-kinin; D010447:Peptide Hydrolases; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D002211:Capsaicin; D001920:Bradykinin