Long‐Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D ₁ Receptor–Mediated Sodium Excretion via Upregulation of G‐Protein–Coupled Receptor Kinase Type 4 Expression in Sprague‐Dawley Rats

Abstract

BackgroundEpidemiological evidence supports an important association between air pollution exposure and hypertension. However, the mechanisms are not clear.Methods and ResultsOur 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, PM 2.5 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 PM 2.5, 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 PM 2.5‐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 PM 2.5‐treated Sprague‐Dawley rats, accompanied by an increase in the low D1 receptor expression, and decreased the hyperphosphorylated D1 receptor and GRK4 expression.ConclusionsOur present study indicated that long‐term exposure of PM 2.5 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 PM 2.5‐induced hypertension.

Inhalation of printer-emitted particles impairs cardiac conduction, hemodynamics, and autonomic regulation and induces arrhythmia and electrical remodeling in rats

“…Dopamine and norepinephrine alter cardiovascular physiology via stimulation of dopaminergic and adrenergic receptors, and can chronically desensitize and/or downregulate these receptors via G-protein receptor kinases (GRKs) and hyper-phosphorylation [65,77,78]. Accordingly, PM can induce hypertension through GRK-mediated desensitization and downregulation of renal D1 dopamine receptors [79], but the role of elevated dopamine remains unknown. Moreover, as β 3 adrenergic and D1 dopamine receptors mediate thermogenesis [65,77], catecholamine elevations may also account for the body temperature increases over the entire 10 weeks following PEPs exposure.…”

Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system

“…Blood lipids, including total cholesterol and triglycerides, were measured by the ELISA kit (Jiancheng, Nanjing, China). The blood pressure and heart rate were also measured at 4, 8, 12, 16, 20, and 24 weeks of age in conscious rats using a computerized noninvasive tail-cuff manometry (BP-98A; Softron, Tokyo, Japan) as described in previous studies [22,23]. Blood pressure and heart rate were measured five times between 3:00–5:00 PM; the average of the five measurements was used in the calculations.…”

In Vitro and In Vivo Experimental Studies of PM2.5 on Disease Progression

“…In PM 2.5 -induced hypertension, long-term PM 2.5 exposure increases blood pressure by inhibiting D1 receptor-related sodium secretion through the regulation of G protein-coupled receptor kinase 4 in Sprague-Dawley Rats. [ 148 ]. In a rat model of gestational diabetes mellitus, PM 2.5 exposure significantly reduced the levels of GSH-Px and induced malondialdehyde, resulting in an oxidative response and inflammation in the pancreas.…”