Disappearance of Hypoxic Pulmonary Vasoconstriction and O<SUB>2</SUB>-Sen-sitive Nonselective Cationic Current in Arterial Myocytes of Rats Under Ambient Hypoxia

Disappearance of Hypoxic Pulmonary Vasoconstriction and O<SUB>2</SUB>-Sen-sitive Nonselective Cationic Current in Arterial Myocytes of Rats Under Ambient Hypoxia

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K<SUP>+</SUP> channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>) and hypoxia-activated nonselective cation channel (I<SUB>NSC</SUB>) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d<SUB>-</SUB>H). Specifically, the associated elec-trophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d<SUB>-</SUB>H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d<SUB>-</SUB>H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d<SUB>-</SUB>H and control. In contrast, hypoxia and TXA<SUB>2</SUB>-activated I<SUB>NSC</SUB> was not observed in PASMCs of 2d<SUB>-</SUB>H. From above results, it is suggested that the decreased I<SUB>NSC</SUB> might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.