INHIBITION OF HYPOXIC PULMONARY VASOCONSTRICTION BY LEUKOTRIENE BLOCKADE

  • 21 February 1986
    • journal article
    • research article
    • Vol. 98  (4) , 113-117
Abstract
The mechanism of hypoxic pulmonary vasoconstriction is still unclear. Since leukotrienes are pulmonary vasoconstrictors and lung cells are able to produce leukotrienes, it has been proposed that leukotrienes are mediators of hypoxic pulmonary vasoconstriction and then inhibition of their synthesis should block hypoxic pressure responses. In order to test this hypothesis we investigated whether diethylcarbamazine (DEC), a known leukotriene synthesis blocker, blocks hypoxic pulmonary vasoconstriction in isolated rat lungs. DEC blocked ongoing and subsequent hypoxic pressure responses in a relatively specific and dose-dependent fashion. We therefore extended our observations to awake rats and found the DEC reversibly inhibited acute hypoxic pulmonary vasoconstriction. Furthermore, pulmonary hypertension and right ventricular hypertrophy in rats exposed to chronic hypobaric hypoxia could be prevented by DEC treatment. From these data we concluded that DEC inhibits both acute and chronic hypoxic pulmonary vasoconstriction. Thus, leukotrienes could be important mediators of hypoxic pulmonary vasoconstriction.