Background: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic pulmonary vasoconstriction (HPV). However, the mechanisms of this physiologic phenomenon are not fully understood. This study was the first to investigate the role of anion exchanger in sustained HPV.Methods: Experiments were performed in the isolated perfused rabbit lung. After preparation, the lungs were divided into six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion exchanger inhibitor)-treated [200 µM (n=5) or 400 µM (n=3)] hypoxic groups, two HCO3- free hypoxic groups, one control hypoxic group (n=7) and one control normoxic group (n=4). DIDS were added to the perfusate at 10 minutes before starting the experiments. In the HCO3- free groups, HEPES (4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid) were added to the perfusate instead of bicarbonate. Furthermore, in the HEPES1 (n=4) and HEPES2 (n=4) groups, the lungs were ventilated with hypoxic gas with or without CO2, respectively.Results: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the acute (0-20 minutes) and sustained (20-60 minutes) phases. No alteration in both phases of HPV was detected by DIDS (200 µM). However, DIDS (400 µM), extended the ascending part of acute HPV until min 24. Both phases of HPV were decreased in the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during the rising part of the acute phase of HPV. Conclusions: Since DIDS (400 µM) extended acute phase of HPV, and HCO3- free perfusate buffer enhanced rising phase of it, therefore it can be suggested that anion exchanger may modulate HPV especially during the acute phase. The abstract of this article was presented as a poster in the congress of European Respiratory Society (ERS) on Monday, 08 September 2014, Munich, Germany and was published in the ERJ September 1, 2014 vol. 44 no. Suppl 58 P2343.