Uric acid was identified as a contributor to pulmonary arterial hypertension (PAH) progression, according to a new study published in the Journal of the American Heart Association.
In vivo studies using rat models with PAH and hyperuricemia showed that the increased levels of uric acid in the lungs of the animals compromised hemodynamics and enhanced occlusive vascular lesions. These effects were inhibited by blocking uric acid transporters (UATs).
“These observations provide insight for the development of novel therapeutic strategies for PAH complicated with hyperuricemia by targeting the UATs,” the authors wrote.
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The UAT inhibitor benzbromarone was used in rats with PAH and hyperuricemia and reduced the levels of uric acid in the lungs without interfering with the activity of xanthine oxidoreductase, an enzyme involved in the synthesis of uric acid. Moreover, it attenuated an increase in right ventricular systolic pressure and the development of an occlusive lesion.
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The authors also observed increased pulmonary vascular resistance (PVR) in perfused lung preparations isolated from rats with PAH. Treatment with arginase or UAT inhibitors (ie, L‐norvaline and benzbromarone, respectively) attenuated PVR. Moreover, they found that uric acid decreased the level of cyclic guanosine monophosphate.
Currently, there is no data regarding the effect of benzbromarone on the hemodynamics of patients with PAH. Its safety and effects on patients’ clinical outcomes remain to be addressed in dedicated clinical studies.
“Further investigations are needed to determine the specific UAT involved in PAH development, and to examine whether inhibition of the specific UAT effectively and safely prevents deterioration in PAH patients with hyperuricemia,” the authors concluded.
Previous studies have shown a positive correlation between serum levels of uric acid and mean pulmonary arterial pressure, disease severity, and prognosis in patients with PAH.
Reference
Watanabe T, Ishikawa M, Abe K, et al. Increased lung uric acid deteriorates pulmonary arterial hypertension. J Am Heart Assoc. Published online November 30, 2021. doi:10.1161/JAHA.121.022712
