Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia.

摘要: To determine whether exposure to chronic hypoxia and subsequent development of pulmonary hypertension induces alterations endothelium-dependent relaxation in rat vascular bed, we studied isolated lung preparations from rats exposed either room air (controls) or (H) during 1 wk (1W-H), 3 (3W-H), 3W-H followed by 48 h recovery (3WH + R). In lungs pretreated with meclofenamate (3 microM), the vasodilator responses acetylcholine (10(-9)-10(-6) M) ionophore A23187 (10(-9)-10(-7) were examined conditions increased tone U46619 (50 pmol/min). Acetylcholine produced dose-dependent vasodilation control lungs, this response was reduced group 1W-H (P less than 0.02), abolished 0.001), restored 3WH R. contrast, endothelium-independent agent sodium nitroprusside remained fully active 3W-H. The pressor 300 pM endothelin greater controls (6.8 +/- 0.5 mmHg vs. 1.6 0.2 mmHg, P 0.001) but not potentiated relaxing factor (EDRF) antagonists: hydroquinone (10(-4) M); methylene blue pyrogallol x 10(-5) as it controls. It similar Our results demonstrate that hypoxia-induced is associated a loss EDRF activity vessels, rapid on return normoxic environment.