The role of histamine in the physiologic alterations of IgE anaphylaxis in the rabbit

Abstract

The respiratory and circulatory alterations induced by intravenous histamine in the pentobarbital anesthetized rabbit were examined and compared to those alterations associated with IgE anaphylaxis following antigen challenge. Histamine induced several graded alterations including an increase in total pulmonary resistance, a decrease in dynamic compliance, an increase in breathing frequency, a decrease in tidal volume, a rise in right ventricular systolic pressure and systemic hypotension. Qualitatively similar alterations occurred during the anaphylactic response, but a quantitative comparison of the two responses revealed that the respiratory alterations in systemic anaphylaxis corresponded to relatively low equivalent histamine doses, whereas the anaphylactic circulatory alterations exceeded the maximum response obtainable with histamine. Pretreatment with H1 antihistamine competitively blocked all of the ventilatory and lung mechanical changes induced by histamine, but it inhibited only the increase in pulmonary resistance induced by antigen. The right ventricular hypertension induced by histamine was also inhibited by H1 antihistamine but the antigen-induced change in this variable was not significantly attenuated. Inhibition of the histamine-induced systemic hypotension required pretreatment with both H1 and H2 histamine antagonists. Such pretreatment, however, did not attenuate the fall in systemic arterial pressure induced by antigen. H1 antihistamine pretreatment prevented histamine- but not antigen-induced lethality. We conclude that histamine is an important mediator of the increase in pulmonary resistance but is not the major mediator of the other physiological alterations of IgE systemic anaphylaxis in the rabbit.