Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.

中文翻译：

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血管扩张剂作为肺动脉高压的潜在药物的氧敏感性和肺选择性

当前批准的肺动脉高压（PH）疗法旨在恢复肺循环中内皮介体之间的平衡。这些药物可能对弱氧血管发挥血管扩张作用。这可能导致血液灌注向低通气的肺泡衍生，即产生通气-灌注不匹配，对气体交换产生不利影响。这项研究的目的是分析目前使用的或可能对PH有用的25种药物的体外氧敏感性。此外，研究还分析了肺血管扩张剂，这些的有效性VS全身血管。在不同的氧气浓度下，通过钢丝肌电图记录了大鼠肺动脉（PA）和肠系膜动脉（MA）以及人PA中的血管舒张反应。所研究的药物均未显示出氧选择性，与低氧水平相比，在低氧条件下与血管扩张剂具有同等或更有效的作用。所研究的药物显示出较低的肺部选择性，与全身用药相比，全身用药与血管扩张剂同等或更有效。对于每个毒品家族中的成员，观察到类似的行为。总之，没有一种药物显示出最佳的血管扩张药谱，这可能会限制其在PH中的治疗效果。