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High Levels of Uric Acid Upregulate Endothelin Receptors: The Role of MAPK Pathways in an in vitro Study

Year: 2024
Type: article
Abstract: Introduction Uric acid (UA) is the end product of purine compounds' metabolism. There is overwhelming evidence linking hyperuricemia (high levels of UA) and cerebrovascular diseases, but the effect of high levels of UA on cerebral vessels is not fully understood. The aim of this research is to clarify how UA affect the endothelin (ET) receptor in rat cerebral arteries and the related mechanism. Material and methods In an in vitro setting, segments of rat cerebral arteries (n=12) were exposed to high levels of UA, either alone or in conjunction with MAPK pathway inhibitors. ET agonists were used to induce contractions that were then measured with a myograph. ET receptor expression was measured using RT-PCR (n=6), Western Blot (n=3), or immunohistochemistry (n=3) to quantify mRNA and protein levels. Results The study revealed that high levels of UA notably increase ETA and ETB receptor-induced contractions and boost the expression of ET receptors in cerebral arteries when compared to that are fresh or cultured alone, suggesting that UA enhances ETA and ETB receptors. Additionally, the up-regulation of ETB receptors induced by UA was inhibited by the p38 inhibitor SB203580, the JNK inhibitor SP600125, and the ERK1/2 inhibitor U0126. SB203580 significantly blocked the increase in ETA receptor-mediated contractions induced by UA and the upregulation of ETA receptor. Neither SP600125 nor U0126 had such effect. Conclusions High levels of UA stimulate the up-regulation of ET receptors in rat cerebral arteries in vitro through MAPK pathways. This study may offer novel perspectives on hyperuricemia-associated cerebrovascular diseases.
DOI: 10.5114/aoms/193455
Language: English
Subfield: Nephrology
Field: Medicine
Open Access status: gold
Estimated APC paid: $1,078
OpenAlex ID: W4403784524
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