title: Adrenal influences on the inhibitory effects of procaterol, a selective Beta-two-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in Guinea pigs.
abstract: While the guinea pig has been the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, it has been shown that antigen-induced bronchoconstriction in guinea pigs is attenuated by epinephrine released from the adrenal gland. In order to investigate the possible influence of the adrenal gland on the effects of antiexudative and bronchodilative drugs on antigen-induced airway responses, we examined the inhibitory effects of procaterol, a selective beta(2)-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in adrenalectomized guinea pigs and compared them with the drug's effects in sham-operated animals. Guinea pigs sensitized passively with anti-ovalbumin (OA) guinea-pig serum were adrenalectomized or sham-operated under urethane anesthesia and examined 30 min after surgery in the following experiments. (1) Animals were intravenously administered Evans blue dye to quantify airway plasma exudation, and then OA was inhaled for 10 min while measuring pulmonary inflation pressure, a parameter of bronchoconstriction. Procaterol (1, 3, 10, or 30 microg/kg) or saline (control) was administered into the airways 10 min prior to OA inhalation. The amount of extravasated Evans blue dye in the airways was calculated. (2) Venous blood samples were collected during OA or saline inhalation and plasma catecholamine levels were compared. In control animals, OA-induced increases in both the amount of Evans blue dye and in pulmonary inflation pressure were markedly greater in adrenalectomized animals than in sham-operated animals. Procaterol dose-dependently inhibited OA-induced airway microvascular leakage and bronchoconstriction, and its effects were more potent in adrenalectomized animals (significant at 1 microg/kg and higher) than in sham-operated animals (significant at 10 microg/kg and higher). Although the plasma concentration of epinephrine during OA inhalation was approximately 3 times higher than that during saline inhalation in sham-operated animals, no difference was seen in adrenalectomized animals. In conclusion, while procaterol essentially possesses pronounced inhibitory effects on antigen-induced airway microvascular leakage and bronchoconstriction in guinea pigs, the effects are considerably masked by epinephrine released from the adrenal gland.
authors.affiliation: Research Institute of Pharmacological and Therapeutical Development, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan. k_ikezono@research.otsuka.co.jp
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ikezono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kamata
authors.forename: Toyoki
authors.initials: T
authors.lastname: Mori
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D000315:Adrenalectomy; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004837:Epinephrine / Q000097:blood; D005070:Evans Blue / Q000008:administration & dosage; D005122:Exudates and Transudates / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006168:Guinea Pigs; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010047:Ovalbumin / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology; D017265:Procaterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018343:Receptors, Adrenergic, beta-2 / Q000008:administration & dosage
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000941:Antigens; D018343:Receptors, Adrenergic, beta-2; D005070:Evans Blue; D010047:Ovalbumin; D017265:Procaterol; D004837:Epinephrine