EDN1 and Hypertension: PER1 gene knockout displays significant sex-dependent differences across various animal models (e.g., mice and rats): male mice show a more pronounced response to KO of PER1, characterized by more severe hypertension and renal injury, whereas female mice remain unaffected (40).Mechanistically, PER1 influences renal sodium handling and blood pressure rhythms by regulating the expression and activity of ET-1, thereby antagonizing salt load-induced vascular contraction and fibrosis.