Paternal long-term PM(2.5) exposure causes hypertension via increased renal AT(1)R expression and function in male offspring

Maternal exposure to fine particulate matter (PM(2.5)) causes hypertension in offspring. However, paternal contribution of PM(2.5) exposure to hypertension in offspring remains unknown. In the present study, male Sprague-Dawley rats were treated with PM(2.5) suspension (10 mg/ml) for 12 weeks and/or fed with tap water containing an antioxidant tempol (1 mM/L) for 16 weeks. The blood pressure, 24 h-urine volume and sodium excretion were determined in male offspring. The offspring were also administrated with losartan (20 mg/kg/d) for 4 weeks. The expressions of angiotensin II type 1 receptor (AT(1)R) and G-protein–coupled receptor kinase type 4 (GRK4) were determined by qRT-PCR and immunoblotting. We found that long-term PM(2.5) exposure to paternal rats caused hypertension and impaired urine volume and sodium excretion in male offspring. Both the mRNA and protein expression of GRK4 and its downstream target AT(1)R were increased in offspring of PM(2.5)-exposed paternal rats, which was reflected in its function because treatment with losartan, an AT(1)R antagonist, decreased the blood pressure and increased urine volume and sodium excretion. In addition, the oxidative stress level was increased in PM(2.5)-treated paternal rats. Administration with tempol in paternal rats restored the increased blood pressure and decreased urine volume and sodium excretion in the offspring of PM(2.5)-exposed paternal rats. Treatment with tempol in paternal rats also reversed the increased expressions of AT(1)R and GRK4 in the kidney of their offspring. We suggest that paternal PM(2.5) exposure causes hypertension in offspring. The mechanism may be involved that paternal PM(2.5) exposure-associated oxidative stress induces the elevated renal GRK4 level, leading to the enhanced AT(1)R expression and its-mediated sodium retention, consequently causes hypertension in male offspring.