Alterations in pulmonary artery tone during repeated episodes of hypoxia

To examine the basis of pulmonary constriction during chronic hypoxia, rat pulmonary artery rings were precontracted and exposed to multiple episodes of hypoxia. The first hypoxic episode resulted in a transient contraction, followed by potent relaxation, and then a slow sustained contraction. Repeated hypoxic exposure resulted in stronger initial contraction and attenuated relaxation. Prolongation of the normoxic interval between hypoxic episodes reversed the attenuation of hypoxic relaxation. Pulmonary artery rings that were deendothelialized or treated with the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester or oxyhemoglobin displayed only hypoxic relaxation without initial or late contractions and no attenuation of relaxation during repeated hypoxia. Pretreatment of rings with indomethacin or adenosine or endothelin receptor antagonists had no effect on the hypoxia-mediated alterations. Thus repetitive exposure to hypoxia results in an increase in initial contraction and a decrease in relaxation of pulmonary artery rings. Frequency of hypoxic episodes and endothelial integrity determine pulmonary tone during repeated hypoxia. However, cyclooxygenase products, adenosine, or endothelin do not play a role in hypoxia-mediated changes in rat pulmonary artery tone.