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 β₂-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 µg/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 µg/kg and higher) than in sham-operated animals (significant at 10 µg/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.

Thymoquinone exhibits anti-inflammatory, antioxidant, and immunomodulatory effects on allergic airway inflammation

“…The inhibitory mechanism of plasma leakage and eosinophil enrichment seems to be closely associated with inhibition of histamine release from mast cells. Previous studies show that microvascular airway leakage is increased in sensitized rats, mice, and guinea pigs by ovalbumin [17,25,[29][30][31][32], and capsaicin [33,34].…”

Treatment Responses of Procaterol and CD38 Inhibitors in an Ozone-Induced Airway Hyperresponsiveness Mice Model

“…Although controversies of anti-inflammation effects remain on other β2 selective agonists, 36,37) numerous pharmacological studies have shown the positive anti-inflammation and bronchodilatory effects of procaterol in murine AHR models. 38,39) A randomized, double-blind, parallel group study in 140 patients with moderate acute asthma also demonstrated that nebulized procaterol is effective in improving peak expiratory flow rate and decreasing the asthma score. 40) Procaterol can inhibit the activation of NF-κB pathway in the previous studies.…”

Low Voltage Vagal Nerve Stimulation Reduces Bronchoconstriction in Guinea Pigs Through Catecholamine Release

“…Parasympathetic pulmonary nerves are normally tonically active and trigger smooth muscle contractions in response to ongoing afferent nerve activity (20,44), while circulating catecholamines have been reported to provide tonal balance (38,45–47). Using adrenalectomy techniques, several investigators (30,48,49) linked these circulating catecholamines to adrenal release and binding to β 2 ‐adrenoceptors to reverse bronchoconstriction. Other studies have indicated a possible impaired sympathoadrenal response to exercise in asthmatics (50,51).…”