Almitrine bismesylate reduces hypoxic pulmonary vasoconstriction in isolated rat lungs

The purpose of this study is to test how almitrine bismesylate (Alm) affects the function of pulmonary vasculature during normoxic ventilation, and whether low doses of Alm not causing detectable vasoconstriction during normoxic ventilation potentiate hypoxic pulmonary vasoconstriction (HPVC). Isolated Wistar male rat lungs were perfused with homologous blood at constant flow, and venous and ventilatory pressure. In the first experiment, after equilibration, dose-response curves to Alm (from 0 to 1000 ng/ml, n = 10) were measured under the ventilation with normoxic gas mixture (21% O2, 5% CO2, 74% N2). It was found that Alm causes a dose-dependent pulmonary vasoconstriction. In the second experiment, low doses of Alm (125 mg/ml) or diluent of Alm (malic acid) was injected to the blood reservoir. This doses of Alm did not cause significant vasoconstriction during normoxic gas ventilation compared with malic acid. After stabilization of pulmonary arterial pressure, the lungs were exposed to three cycles of normoxia (10 min) and hypoxia (10 min) through ventilation with gas containing 21% or 2% O2 and 5% CO2. It was observed that low doses of Alm significantly reduce HPVC (p less than 0.05) on the later periods of the first and the second hypoxic challenges. However, no significant difference was revealed among two groups in the third hypoxic challenge. Directly measured blood Alm concentration was significantly lower in the third challenge than in the first challenge. Responses to angiotensin II were not decreased by Alm. In conclusion, high doses of Alm constrict pulmonary vasculature dose-dependently, and low doses of the drug not causing vasoconstriction during normoxia reduce HPVC in rat.