We demonstrate that 1) acute injection of AEA did not affect blood pressure in conscious Dahl SS rats; 2) chronic treatment with a low dose of AEA (0.05 mg/kg) did not modulate blood pressure or kidney function during the development of SS hypertension; 3) a high dose of AEA (3 mg/kg daily) led to a significant aggravation of hypertension and profound renal damage after chronic administration; 4) the negative effect of chronic treatment with AEA was correlated with the upregulated Smad3 intracellular pathway. This evidence concerns the gene SMAD3 and hypertensive disorder.