Long-Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D Receptor-Mediated Sodium Excretion via Upregulation of G-Protein-Coupled Receptor Kinase Type 4 Expression in Sprague-Dawley Rats.

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 (PM) causes hypertension and impairs renal sodium excretion, which might be ascribed to lower D receptor expression and higher D 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, PM increased basal and decreased D receptor mediated inhibitory effect on Na-K ATPase activity, decreased D receptor expression, and increased D receptor phosphorylation in renal proximal tubule cells). The downregulation of D receptor expression and function might be attributable to a higher GRK4 expression after the exposure of renal proximal tubule cells to PM, because downregulation of GRK4 by small-interfering RNA reversed the D receptor expression and function. Because of the role of reactive oxygen species on D receptor dysfunction and its relationship with air pollution exposure, we determined plasma reactive oxygen species and found the levels higher in PM-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 PM-treated Sprague-Dawley rats, accompanied by an increase in the low D receptor expression, and decreased the hyperphosphorylated D receptor and GRK4 expression.

Conclusions: Our present study indicated that long-term exposure of PM increases blood pressure by decreasing D receptor expression and function; reactive oxygen species, via regulation of GRK4 expression, plays an important role in the pathogenesis of PM-induced hypertension.