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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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Alveolar hypoxia induces monophasic pulmonary vasoconstriction in vivo, biphasic vasoconstriction in the isolated pulmonary artery, and controversial responses in the isolated perfused lung. Pulmonary vascular responses to sustained alveolar hypoxia have not been addressed in the isolated perfused rat lung. In this study, we investigated the effect of sustained hypoxic ventilation on pulmonary artery pressure in the present of phenylephrine, an α1-receptor agonist, under the above condition. Methods: We performed this study in the isolated perfused rat lung. After preparation, the lungs were divided randomly into five groups of normoxic-normocapnia, hypoxic-normocapnia, phenylephrine pre- or post-treated hypoxic-normocapnia and phenylephrine pre-treated normoxic-normocapnia. Pulmonary hemodynamic, airway pressure and lung weight were measured during 60 min of the experiment for each group. Results: In the phenylephrine-pre-treated hypoxic-normocapnia group we observed a gradual increase in pulmonary artery pressure which approximated the results seen in the phenylephrine-pre-treated normoxic-normocapnia group. In contrast, in the phenylephrine-post-treated hypoxic-normcapnic group, pulmonary artery pressure did not change during the first 3 min of hypoxic-normocapnia. However at 1.5 min after administration of phenylephrine, this pressure began to increase sharply and continued until the end of the experiment. This response was biphasic (0-10 min: acute phase, 10-60 min: sustained phase) with significantly higher pulmonary artery pressure compared to the other groups. Conclusion: This study, for the first time, showed biphasic hypoxic pulmonary vasoconstriction in the isolated perfused rat lung with the sole administration of phenylephrine after but not before hypoxic gas ventilation. This finding suggested a facilitative role of alveolar hypoxia on pulmonary vasoconstriction induced by an α1-receptor agonist. [ABSTRACT FROM AUTHOR]

Background: Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats. Methods: This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey's post hoc test and t test, was used to compare the variables in the experimental groups. Results: The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO2 and pH were lower, and PCO2 was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019). Conclusion: Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing. [ABSTRACT FROM AUTHOR]

Background: The mechanism of hypoxic pulmonary vasoconstriction (HPV) is still debatable. It has been proposed that reactive oxygen species (ROS) might be involved in HPV. However, there is no special transporter for superoxide anion in the cell membrane and it may release from the cells via anion exchanger. Therefore, the aim of this study was to investigate the interaction of ROS and anion exchanger in acute HPV. Methods: The present study was performed in the isolated rabbit lung. After preparation, the lungs were divided into four hypoxic groups of control, Trolox (antioxidant)-treated, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, anion exchanger inhibitor)-treated, and Trolox+DIDS-treated. Pulmonary artery pressure, left atrial pressure, and lung weight were continuously registered and PVR was then calculated. PO2, PCO2, HCO3-, pH, and NO metabolites of the perfusate were measured during steady-state and at the end of experiments (30 minutes). All data were compared with ANOVA and t-test and significance was considered when P<0.05. Results: Ventilation ofthe lungs with hypoxic gas induced HPV in the control group. DIDS did not have a further effect on HPV compared with the control group. The combination of Trolox and DIDS decreased HPV rather than Trolox per se at 5 minutes. Furthermore, HPV was abolished in both the Trolox and Trolox+DIDS groups at 30 minutes. Concentrations of NO metabolites in the Trolox+DIDS group were more than other groups. Conclusion: The present study indicates a possible interaction between ROS and anion exchanger in acute HPV. It also suggests the modulatory effect of NO at above condition. [ABSTRACT FROM AUTHOR]

Background: Alveolar hypoxia induces monophasic pulmonary vasoconstriction in vivo, biphasic vasoconstriction in the isolated pulmonary artery, and controversial responses in the isolated perfused lung. Pulmonary vascular responses to sustained alveolar hypoxia have not been addressed in the isolated perfused rat lung. In this study, we investigated the effect of sustained hypoxic ventilation on pulmonary artery pressure in the present of phenylephrine, an α1-receptor agonist, under the above condition., Methods: We performed this study in the isolated perfused rat lung. After preparation, the lungs were divided randomly into five groups of normoxic-normocapnia, hypoxic-normocapnia, phenylephrine pre- or post-treated hypoxic-normocapnia and phenylephrine pre-treated normoxic-normocapnia. Pulmonary hemodynamic, airway pressure and lung weight were measured during 60 min of the experiment for each group., Results: In the phenylephrine-pre-treated hypoxic-normocapnia group we observed a gradual increase in pulmonary artery pressure which approximated the results seen in the phenylephrine-pre-treated normoxic-normocapnia group. In contrast, in the phenylephrine-post-treated hypoxic-normcapnic group, pulmonary artery pressure did not change during the first 3 min of hypoxic-normocapnia. However at 1.5 min after administration of phenylephrine, this pressure began to increase sharply and continued until the end of the experiment. This response was biphasic (0-10 min: acute phase, 10-60 min: sustained phase) with significantly higher pulmonary artery pressure compared to the other groups., Conclusion: This study, for the first time, showed biphasic hypoxic pulmonary vasoconstriction in the isolated perfused rat lung with the sole administration of phenylephrine after but not before hypoxic gas ventilation. This finding suggested a facilitative role of alveolar hypoxia on pulmonary vasoconstriction induced by an α1-receptor agonist.