Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways.

Abstract

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.

• Authors: I Yamawaki, J Tamaoki, Y Takeda, A Chiyotani, N Sakai, S Kameyama, K Konno
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 79 Issue 4 Pg. 1129-33 (Oct 1995) ISSN: 8750-7587 [Print] United States
• PMID: 8567553 (Publication Type: Journal Article)

Chemical References

• Bradykinin Receptor Antagonists
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Tachykinins
• 3-(2-methoxybenzylamino)-2-phenylpiperidine
• T-kinin
• Peptide Hydrolases
• Peptidyl-Dipeptidase A
• Neprilysin
• Capsaicin
• Bradykinin

Topics

• Amino Acid Sequence
• Animals
• Blood Pressure (drug effects)
• Bradykinin (analogs & derivatives, pharmacology)
• Bradykinin Receptor Antagonists
• Capillary Permeability (drug effects)
• Capsaicin (pharmacology)
• Dose-Response Relationship, Drug
• Heart Rate (drug effects)
• Male
• Molecular Sequence Data
• Neprilysin (metabolism)
• Neurokinin-1 Receptor Antagonists
• Neurons, Afferent (drug effects)
• Peptide Hydrolases (physiology)
• Peptidyl-Dipeptidase A (metabolism)
• Piperidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Respiratory System (blood supply, drug effects, enzymology)
• Tachykinins (pharmacology)