[Method for evaluating pulmonary clearance in mice and its pharmacological applications].
The purpose of this study was to develop a method for evaluating pulmonary clearance in mice that inhaled aerosolized 99mTc-labeled human serum albumin (33mTc-HSA). Mice were ventilated with an aerosol of 99mTc-HSA for 10 min with an ultrasonic nebulizer in an acrylic chamber. Pulmonary clearance was estimated from lung retention ratio at various times after inhalation of 99mTc-HSA. Lung retention ratios in mice were 72.4 +/- 3.3% at 1 hr, 60.1 +/- 2.3% at 3 hr and 34.8 +/- 2.0% at 24 hr after inhalation of 99mTc-HSA, similar to the previous results obtained in humans by cinescintigraphy. The data were analyzed on the basis of two-compartment model. Mabuterol, a beta 2-adrenoceptor agonist, stimulated the pulmonary clearance. In contrast, metyrapone, an adrenal 11-beta steroid hydroxylase inhibitor, suppressed the clearance with a decreased corticosterone content in plasma. These findings suggest that the developed method is useful for evaluating the pharmacological effects on pulmonary clearance.
Kai
H
H
Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Ishibashi
A
A
Takahama
K
K
Sakata
K
K
Isohama
Y
Y
Nakayama
M
M
Sugii
A
A
Miyata
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002976:Clenbuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008722:Methods; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D013668:Technetium Tc 99m Aggregated Albumin
D000318:Adrenergic beta-Agonists; D013668:Technetium Tc 99m Aggregated Albumin; C044573:mabuterol; D002976:Clenbuterol; D008797:Metyrapone