Diethylcarbamazine inhibits acute and chronic hypoxic pulmonary hypertension in awake rats.

Abstract

Leukotriene inhibitors preferentially inhibit the acute pressor response to hypoxia in isolated rat lungs. If leukotrienes are important in hypoxic pulmonary vasoconstriction, then inhibition of their synthesis could prevent the development of chronic hypoxic pulmonary hypertension. We found that diethylcarbamazine (DEC), a leukotriene synthesis blocker, reversibly inhibited acute hypoxic pulmonary vasoconstriction in the awake rat. Rats exposed to chronic hypobaric hypoxia showed pulmonary hypertension and the production of a slow-reacting substance compared with low altitude control rats. The higher of 2 doses of DEC blocked the pulmonary hypertension and the production of slow-reacting substance in all of the hypoxic rats treated. The lower dose of DEC attenuated the pulmonary hypertension in only some of the rats. Changes in weight gain, hematocrit, or generation of prostacyclin did not explain the prevention of the pulmonary hypertension by DEC. We conclude that diethylcarbamazine inhibits acute and chronic pulmonary hypertension in the intact rat.