Effect Of Long-term Exposure Of Paternal Rats To Fine Particulate Matter On Blood Pressure And Natriuresis In The Offspring

BackgroundEssential Hypertension?EH?is one of the most common diseases which is a great threat to mankind health for a long time.Since the incidence and mortality rates of EH rise gradually,and the average age of incidence has the trend of rejuvenation along with the advancement of the medicine.it's extremely fulfilling for the prevention and treatment of hypertension to make its etiology and pathogenesis clear.Hypertensionthe is the result of interaction of various complicated factors,such as inheritance,individual life and environment factors.Currently,environment factors especially air pollution has caused attention.Fine particulate matter(PM_2.5),which is a kind of inhaled small suspended particles whose diameter is less than 2.5?m in the atmosphere,is showed to be closely related with hypertension.It shows that exposure to diesel exhaust air pollution in utero could result in weight gain,blood pressure altered,and heart failure in adult offspring.PM_2.5 also could influence reproductive system when Fathers long-term exposure to hostile environment like smoking or motor vehicle exhaust,which leads to bronchial asthma,metabolic disorders of the offspring.But it's not clear whether it effects the blood pressure of the offspring when paternal exposure to PM_2.5.In the early experiment We found that the blood pressure in the offspring whose father received PM_2.5 for 12 weeks is higher than the control group.It showed that paternal exposure to PM_2.5 probably cause higher blood pressure in children.But he mechanism remains unclear.Kidney is one of the important organs which regulate blood pressure by water sodium reabsorption.It reported that G protein-coupled receptor kinase 4?GRK4?,mainly in the kidney,has higher expression and activity in the hypertension patients and spontaneously hypertensive rats.It could cause hypertension by adjusting the expression or phosphorylation of dopamine receptors especially dopamine 1 subtype to alter the activity of Na+-K+-ATPase and then lead to the dysfunction of urinary sodium excretion.Previous animal experiments showed that PM_2.5 could indeed elevate blood pressure probably by altering GRK4 protein in kidney,thus,the urinary sodium excretion function of D₁ receptor was deprived.From the above,PM_2.5 suspension was administered by intratracheal instillation to establish the animal model to preliminary observation the effect of long-term exposure of paternal rats to PM_2.5 on the blood pressure in the offspring and the relationship with urinary sodium excretion in kidney.ObjectTo determine the effect of paternal rats long-term exposure to fine particulate matter on blood pressure and natriuresis in the offspring.Method1.Male SD rats were supplied PM_2.5 suspension by intra-tracheal instillation,and the control group with the equal dose of phosphate buffered saline?PBS?for 12 weeks.HE staining of lung tissues,weight,blood pressure,and 24 hours urinary sodium excretion of rats were used to evaluate the feasibility of the model.2.The offspring which came from the two group of male rats bred by health female SD rats after 12 weeks were fed to 7 weeks of age.The basic blood pressure and 24 hours urinary sodium excretion were observed in the offspring.Then fenoldopam was perfused through suprarenal artery administration to determined the natriuresis function of D₁ R.3.Western blot was performed to evaluate the protein levels of renal GRK4 and D₁ R of the offspring.Result1.Significant changes were observed in the blood pressure and natriuresis in basic condition of exposed rats after 12 weeks intervention.The lung tissue samples showed the deposit of particulate matter,which indicated that the animal model was feasible.2.Compared with the control,the basic blood pressure in the exposed offspring was higher at 7 and 9 weeks of age and the natriuresis were significantly inhibited in the exposed offspring.3.GRK4 expression of kidney cortex was increased,and D₁ R protein was reduced in rat offspring after paternal exposure to PM_2.5.ConclusionLong-term exposure of paternal rats to PM_2.5 could elevate blood pressure in the offspring,that probably be concerned with the overexpression of GRK4 which leads to the natriuresis dysfunction of D₁R.