Tolbutamide reverses hypoxic pulmonary vasoconstriction in isolated rat lungs.

We have investigated the effects of tolbutamide on the hypoxic vasoconstriction of isolated, perfused rat lungs. We did this because lowered ATP may link hypoxia and constriction, and tolbutamide mimics the effects of ATP in other tissues by blocking ATP-sensitive potassium (ATP-K) channels. Pulmonary vasoconstriction, induced by lowering the oxygen of the gas ventilating the lungs from 95 to 2%, was always reduced or abolished by tolbutamide (1.7 x 10(-4)-8.5 x 10(-3) M). High concentrations (greater than or equal to 10(-3) M) of diazoxide, a drug that opens ATP-K channels, dramatically constricted the pulmonary vasculature and this effect was also reversed by tolbutamide. The opening of ATP-K channels may therefore underlie hypoxic pulmonary vasoconstriction.