Ascaris-Induced Respiratory Responses in the Conscious Rhesus Monkey

Abstract

Reproducible immediate-type respiratory responses were evoked in conscious monkeys, sensitive to inhaled Ascaris suum, for periods up to 18 months. These responses were characterized by decreases in tidal volume and increases in breathing rate that persisted for about 40 min. Maximum changes were seen 3–5 min after exposure to the aerosolized antigen and were often accompanied by coughing and increased movement of the animals within the plethysmograph used for monitoring their ventilatory changes. Significant inhibition of the Ascaris-induced respiratory changes were seen in animals treated with either isoproterenol or cromolyn sodium. However, the latter agent was not effective in reversing histamine-induced ventilatory changes. The conscious monkey appears to be a suitable animal for evaluating potential antiallergic drugs.

Separation of bronchoconstriction from increased ventilatory drive in a nonhuman primate model of chronic allergic asthma

“…PC30, provocative allergen concentration that induced a 30% increase; PC50, provocative allergen concentration that induced a 50% increase; NA, not achieved within the doses tested. *Different from the histamine response in the absence of salbutamol, P Ͻ 0.008. on this subpopulation of animals with prolonged Ascaris sensitivity, Weissberg and Garay (22) documented early-phase changes in RR and VT to Ascaris antigen for up to 1.5 yr after the initial sensitization. Plopper and colleagues demonstrated that sensitization of neonatal rhesus monkeys to dust mite and subsequent chronic exposure to dust mite allergen and ozone results in expression of asthma features for up to 6 mo (3,7,11,18,20).…”

“…A potential role for mast cell-derived histamine release. Mast cell activation and histamine release were thought to play a major role in the early response to allergen, and a previous study in Ascaris -sensitive rhesus monkeys demonstrated that mast cell stabilization by DSCG attenuated the allergen-induced increase in RR and decrease in VT (22). The ability of aerosolized DSCG to inhibit the changes in breathing pattern after low-level allergen provocation was therefore investigated.…”

“…Effect of ␤-adrenergic agonists on induced respiratory drive. ␤-Adrenergic agonists had been shown to reduce allergen-induced changes in RR and VT in Ascaris -sensitive rhesus macaques (22). The effect of ␤-adrenergic agonists on the ventilatory responses to allergen and histamine was therefore investigated.…”

“…The increase in ventilatory drive after allergen challenge is inhibited by disodium cromoglycate, indicating that mast cell release of histamine underlies the response (22). Furthermore, ␤-adrenergic agonists inhibit increases in RR after both allergen challenge (22) and direct histamine provocation (4,6).…”

“…The increase in ventilatory drive after allergen challenge is inhibited by disodium cromoglycate, indicating that mast cell release of histamine underlies the response (22). Furthermore, ␤-adrenergic agonists inhibit increases in RR after both allergen challenge (22) and direct histamine provocation (4,6). However, histamine and ␤-adrenergic receptors are expressed on both smooth muscle cells and neurons within the airways, making it unclear whether the stimulation of ventilatory drive by histamine is due to a direct effect on sensory receptors or a secondary effect of bronchoconstriction.…”