Long-Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D1 Receptor-Mediated Sodium Excretion via Upregulation of G-Protein-Coupled Receptor Kinase Type 4 Expression in Sprague-Dawley Rats.
Journal of the American Heart Association
BACKGROUND: Epidemiological evidence supports an important association between air pollution exposure and hypertension. However, the mechanisms are not clear.
METHODS AND RESULTS: Our present study found that long-term exposure to fine particulate matter (PM2.5) causes hypertension and impairs renal sodium excretion, which might be ascribed to lower D1 receptor expression and higher D1 receptor phosphorylation, accompanied with a higher G-protein-coupled receptor kinase type 4 (GRK4) expression. The in vivo results were confirmed in in vitro studies (ie, PM2.5 increased basal and decreased D1 receptor mediated inhibitory effect on Na+-K+ ATPase activity, decreased D1 receptor expression, and increased D1 receptor phosphorylation in renal proximal tubule cells). The downregulation of D1 receptor expression and function might be attributable to a higher GRK4 expression after the exposure of renal proximal tubule cells to PM2.5, because downregulation of GRK4 by small-interfering RNA reversed the D1 receptor expression and function. Because of the role of reactive oxygen species on D1 receptor dysfunction and its relationship with air pollution exposure, we determined plasma reactive oxygen species and found the levels higher in PM2.5-treated Sprague-Dawley rats. Inhibition of reactive oxygen species by tempol (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) reduced blood pressure and increased sodium excretion in PM2.5-treated Sprague-Dawley rats, accompanied by an increase in the low D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression.
CONCLUSIONS: Our present study indicated that long-term exposure of PM2.5 increases blood pressure by decreasing D1 receptor expression and function; reactive oxygen species, via regulation of GRK4 expression, plays an important role in the pathogenesis of PM2.5-induced hypertension.
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Lu, X., Ye, Z., Zheng, S., Ren, H., Zeng, J., Wang, X., Jose, P., Chen, K., & Zeng, C. (2018). Long-Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D1 Receptor-Mediated Sodium Excretion via Upregulation of G-Protein-Coupled Receptor Kinase Type 4 Expression in Sprague-Dawley Rats.. Journal of the American Heart Association, 7 (1). http://dx.doi.org/10.1161/JAHA.117.007185