Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways.
To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (RL) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For comparison, responses after 1 microgram/kg substance P were also examined. After measurement of RL, microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30 micrograms/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.
Arakawa
H
H
Department of Pediatrics, Gunma University School of Medicine, Japan.
Tokuyama
K
K
Yokoyama
T
T
Mochizuki
H
H
Morikawa
A
A
Kuroume
T
T
Barnes
P J
PJ
D000375:Aging / Q000502:physiology*; D000402:Airway Obstruction / Q000139:chemically induced* / Q000503:physiopathology; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000098:blood supply / Q000254:growth & development*; D002199:Capillary Permeability / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000254:growth & development* / Q000502:physiology; D008297:Male; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000254:growth & development*
D013373:Substance P; D005070:Evans Blue; D006632:Histamine