Role of histamine in the hypoxic vascular response of the lung

The lung vasculature responds to alveolar hypoxia by constriction and when the hypoxia is localized to one region of the lung, vasoconstriction is also localized to that region. Histamine has been alleged to have a role in the vasoconstrictor response with generalized alveolar and thus systemic hypoxia, but the role for histamine is not clear in localized alveolar hypoxia. Studies were, therefore, undertaken to determine the contribution of histamine to the localized pulmonary vasoconstrictor response to hypoxia. A divided tracheal cannula was used in anesthetized dogs which allowed for ventilation of one lung with oxygen to maintain normal systemic oxygenation (mean PaO2 =73 mm Hg) while the other lung was ventilated with nitrogen as an alveolar hypoxic stimulus. Perfusion to each lung was determined with the 133Xe technique utilizing external counters over the chest. Perfusion (Q) was decreased by 32% (P = 0.002) to the hypoxic lung after 10 minutes of unilateral nitrogen breathing. After intravenous infusion of 20 mg of chlorpheniramine maleate, a potent antihistamine, the decrease in Q to the hypoxic lung was unchanged at 30%. After 40-100 mg chlorpheniramine the decrease in perfusion was again unchanged at 34%. Therefore a significant role was not demonstrated for histamine in the regional pulmonary vasoconstrictor response to alveolar hypoxia in the absence of systemic hypoxemia.