In-utero cold stress causes elevation of blood pressure via impaired vascular dopamine D₁ receptor in offspring

Objective:Environmental cold stress is an important factor that leads to hypertension. The role and the mechanisms of in-utero cold stress in hypertension in adult offspring remain unknown.Methods: The pregnant rats were housed in cold (4°C) rooms from 14 to 21 days of gestation for prenatal cold exposure. The blood pressure and vascular response offspring of control and cold exposure were measured. And the receptor expression, phosphorylation and internalization were checked by immunoblotting or immunoprecipitation.Results: In the present study, we report that prenatal cold stress elevated the blood pressure via decreasing D₁ receptor-associated vasodilation, which is ascribed to decreased D₁ receptor expression and function. Moreover, the artery G protein-coupled receptor kinase 4 (GRK4) expression has been found to be higher in the prenatal cold stress treated offspring than the controls, which could cause the increased phosphorylation and internalization of D₁ receptor in mesenteric artery from prenatal cold stress treated offspring, and led to receptor desensitization and vascular dysfunction.Conclusion: The results illustrate a new paradigm for the developmental origins of hypertension and imply that GRK4 and dopamine D₁ receptor may be crucial determinants for the maternal hypertension.