Abstract
An intact dopaminergic system is necessary to maintain normal blood pressure. We have reported that D2 dopamine receptor (D2R) regulates renal reactive oxygen species (ROS) production and that altered D2R function results in ROS‐dependent hypertension. Paraoxonase 2 (PON2) belongs to the paraoxonase gene family that is expressed in various tissues including the kidney and protects against cellular oxidative stress.We hypothesized that PON2 may be involved in counter‐regulating excessive renal ROS production and thus may contribute to maintain normal blood pressure. Moreover, D2R may regulate ROS production in part through regulation of PON2. ROS production decreased (42%; P<0.05; n=4) in human renal proximal tubular (iNT) cells treated with the D2R agonist, quinpirole (24h, 1μM). This effect was associated with increased PON2 expression of mRNA and protein and enzymatic activity. PON‐2 silencing (siRNA, 10nM, 48h) down‐regulated PON2 expression (50%; n=3) and activity and increased ROS (34.9%, P<0.05). Furthermore, renal PON2 expression was down‐regulated in D2−/− mice (35.6%, P<0.05).These results show that PON2 expression and/or function are closely related to ROS production and suggest that the D2R is involved in its regulation. The increased oxidative stress due to D2R disruption could be related to the failure of its stimulatory effect on the expression or function of PON2 in the kidney.This work was supported in part by grants from the National Institutes of Health, HL68686, HL23081, HL074940, HL092196 and DK39308
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call