Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase.
To study the effect of maturation on bradykinin-induced airflow obstruction and airway microvascular leakage, we measured changes in both lung resistance (RL) and extravasation of Evans Blue dye in anaesthetized immature (aged 12 +/- 1 days) and adult guinea-pigs (aged 77 +/- 2 days). After measurement of RL after i.v. administration of bradykinin (2.5, 5 and 10 nmol/kg) or vehicle (0.9% NaCl), dye extravasation in the lower airways was examined in the same animal. Bradykinin did not cause a significant increase in RL in immature airways, whereas even 2.5 nmol/kg induced a significant elevation in adult airways. Bradykinin-induced extravasation of Evans Blue dye was greater in adult than in immature animals. Phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, did not abolish the age-related difference in the amount of dye extravasated, suggesting that mechanisms other than changes in neutral endopeptidase activity may be responsible for the lower potency of bradykinin in inducing airway microvascular leakage in immature airways.
Yokoyama
T
T
Department of Pediatrics, Gunma University School of Medicine, Japan.
Tokuyama
K
K
Morikawa
A
A
Kuroume
T
T
D000375:Aging / Q000502:physiology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D006020:Glycopeptides; D005070:Evans Blue; D015260:Neprilysin; D001920:Bradykinin; C008890:phosphoramidon