LOSS OF ENDOTHELIUM-DEPENDENT RELAXANT ACTIVITY IN THE PULMONARY CIRCULATION OF RATS EXPOSED TO CHRONIC HYPOXIA

To determine whether exposure to chronic hypoxia and subsequent development of pulmonary hypertension induces alterations of endothelium-dependent relaxation in rat pulmonary studied isolated lung preparations from rats exposed to either room air (controls) or hypoxia (H) during 1 wk (3W-h), 2 wk (3W-H), or 3W-H followed by 48 h recovery to room air (3WH + R). In lungs pretreated with meclofenamate (3 mu-M), the endoth elium-dependent vasodilator responses to acetylcholine (10-9-10-6M) and ion ophore A23187(10-(-10-7M) were examined during conditions of increased tone by U46619 (50 pmol0min). Acetylcholine or A23187 produced dose-dependent v asodilation in control lungs, this response was reduced in group 1W-H (P le less-than 0.02), abolished in group 3W-H than in controls (6.8 +/- 0.5 mmHg vs 1.6 +/- 0.2 mmHg, P less-than 0.001) but was not potentiated by the end endothelium-dependent relaxing factor (EDRF) antagonists: hydroquinone (10- 4M); methylene blue (10-4M); and pyrogallol (3 x 10-5M) as it was in controls. It was similiar to controls in group 3W-H + R. Our results demonstrate that hypoxia-induced pulmonary hypertension is associated with a loss of EDRF activity in pulmonary vessels, with a rapid recovery on return to a normoxic environment.