Author + information
- Xi Lu and
- Chunyu Zeng
Epidemiological evidence supports an important association between air pollution exposure and hypertension. However, the mechanisms are not clear. We examined the association between fine particulate matter (PM2.5) exposure and hypertension as well as impairs renal sodium excretion
We exposed Sprague-Dawley (SD) rats to PM2.5 in vivo and exposed immortalized renal proximal tubule (RPT) cells in vitro, then test dopamine D1 receptor expression and function. Further more, we studied the role of reactive oxygen species (ROS) in the pathogenesis of PM2.5-induced hypertension.
The in-vivo results were confirmed in in-vitro studies, i.e. 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 RPT cells. The downregulation of D1 receptor expression and function might be due to a higher G protein-coupled receptor kinase type 4 (GRK4) expression after the exposure of RPT cells to PM2.5, since down-regulation of GRK4 by siRNA reversed the D1 receptor expression and function. Due to the role of ROS on D1 receptor dysfunction and its relationship with air pollution exposure, we determined plasma ROS, and found the levels higher in PM2.5 treated SD rats. Inhibition of ROS by tempol reduced blood pressure and increased sodium excretion in PM2.5 treated SD rats, accompanied by an increase in the low D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression.
Our present study indicated that long-term exposure of PM2.5 increases blood pressure by decreasing D1 receptor expression and function; ROS, via regulation of GRK4 expression, plays an important role in the pathogenesis of PM2.5-induced hypertension.