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The profile of histamine responsiveness of the pulmonary circulation and the role of endogenous histamine in regulating pulmonary vascular tone and reactivity were studied using the isolated perfused feline pulmonary circulation. Repetitive cumulative dose-response curves demonstrated a progressive decline in the response of the pulmonary circulation to histamine. The present studies also demonstrated elaboration of histamine by the perfused feline lung, and showed that decreasing this elaboration by mast-cell stabilization with cromolyn sodium (disodium cromoglycate, DSCG) had no significant effect on pulmonary vascular tone but resulted in greater lobar vasoconstriction to infused histamine. In contrast, DSCG had no significant effect on the pulmonary pressor response to serotonin, norepinephrine, hypoxia, and hypercapnia. These data suggest that 1) pulmonary; vascular tachyphylaxis occurs with exogenously infused histamine; 2) the withdrawal of endogenous histamine results in greater pulmonary vasoconstriction to exogenously infused histamine; an 3) the histamine release, which was prevented by DSCG, has no role in mediating pulmonary hypoxic or hypercapnic vasoconstriction in the cat.

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