CAPSAICIN AND HISTAMINE ANTAGONIST-SENSITIVE MECHANISMS IN THE IMMEDIATE ALLERGIC REACTION OF PIG AIRWAYS

The airway vascular and bronchial responses were studied in pigs sensitized with Ascaris suum. Ascaris, histamine (H) and capsaicin aerosol all induced a clear-cut increase in blood flow in the nasal, laryngeal and bronchial circulation with a decrease in vascular resistance of 20-40%. When delivered to the lung both ascaris and histamine, but not capsaicin, caused pulmonary airflow obstruction with increase in resistance and a fall in dynamic compliance of 40-70%. After pretreatment of pigs with a combination of the H1- and H2-receptor antagonists terfenadine and cimetidine, the vascular and bronchial responses were strongly reduced to both histamine (by >77%) and ascaris (by >58%), but not to capsaicin aerosol. The bronchoconstriction to histamine was found to be mediated by H1-receptors only, while both H1- and H1-antagonists were necessary to block the vasodilatory response, with H2-receptors being more important in the bronchial circulation and H1-receptors being more important in the laryngeal and nasal circulation. Furthermore, when pigs were pretreated with capsaicin systemically 2 days before the experiment, the vasodilatation was decreased upon capsaicin (by 80%), ascaris (by >40%) and histamine (by >50%) aerosol challenge. When histamine was administered intravenously the desensitizing effect of capsaicin pretreatment was much less pronounced. The effect of capsaicin desensitization on the pulmonary obstruction upon ascaris and histamine challenge was limited to a 60% reduction of the fall in dynamic compliance and a delayed peak in resistance upon ascaris challenge. We conclude that histamine is one of the main vasodilatory mediators released upon allergen challenge at three different levels of the pig airways. A considerable part of the histamine effect is indirect and probably due to activation of capsaicin-sensitive sensory nerves.