A novel method for the evaluation of bronchoactive agents in the conscious guinea pig.
We describe a simple, noninvasive, nontraumatic and reproducible method in which the activities of bronchoactive agents may be recorded in six conscious guinea pigs simultaneously. The method involves the use of "head out" whole body plethysmographs from which respiratory rate can be recorded, by monitoring respiration-related changes in pressure within the body chamber. Exposure of a guinea pig to an aerosolised bronchoconstrictor agent causes an increase in respiratory rate, which is quantified by measuring the area under the respiratory rate curve using a purpose-built respiratory computer. This can be carried out for six animals simultaneously and independently. When exposed to a standard bronchoconstrictor aerosol challenge at intervals over a 6 hr period, the areas under the respiratory rate curves for each animal are highly reproducible. Inhalation of nebulized solutions of acetylcholine (ACh), histamine (Hist), 5-hydroxytryptamine, bradykinin, leukotriene D4 and the thromboxane A2-mimetic, U-46619, but not prostaglandin F2 alpha (PGF2 alpha) caused dose-related bronchoconstriction observed as increases in respiratory rate. In addition, salbutamol, clenbuterol, N-ethylcarboxamide adenosine (NECA) and PGE2 all inhibited ACh (1 mg mL-1) and Hist (1 mg mL-1)-induced increases in respiratory rate in a dose-related fashion. The method described, which is both noninvasive and nontraumatic, may therefore be used to quantify in the conscious guinea pig, both bronchoconstrictor and bronchodilator agents.
Ball
D I
DI
Department of Peripheral Pharmacology, Glaxo Group Research, Ware, Herts, UK.
Coleman
R A
RA
Hartley
R W
RW
Newberry
A
A
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001273:Atmosphere Exposure Chambers; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D006168:Guinea Pigs; D010993:Plethysmography, Whole Body; D015203:Reproducibility of Results; D012119:Respiration / Q000187:drug effects*
D000336:Aerosols; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents