Curcumin Exerts its Anti-hypertensive Effect by Down-regulating the AT(1) Receptor in Vascular Smooth Muscle Cells

Curcumin exerts beneficial effects on cardiovascular diseases, including hypertension. However, its mechanisms are unknown. We propose that curcumin prevents the development of hypertension by regulating AT(1) receptor (AT(1)R) expression in arteries. The present study examined how curcumin regulates AT(1)R expression in vascular smooth muscle cells and investigated the physiological significance of this regulation in angiotensin (Ang) II-induced hypertension. The results showed that curcumin decreased AT(1)R expression in a concentration- and time-dependent manner in vascular smooth muscle cells. Using luciferase reporters with an entire AT(1) or a mutant AT(1)R in A10 cells, the AT(1)R promoter activity was inhibited by 10(−6 )M curcumin, and the proximal element (from −61 to +25 bp) of the AT(1)R promoter was crucial for curcumin-induced AT(1)R down-regulation. An electrophoretic mobility shift assay showed that curcumin decreased specificity protein 1 (SP1) binding with the AT(1)R promoter in A10 cells. Curcumin treatment reduced Ang II-induced hypertension in C57Bl/6J mice, which was accompanied by lower AT(1)R expression in the arteries and decreased Ang II-mediated vasoconstriction in the mesenteric artery. These findings indicate that curcumin down-regulates AT(1)R expression in A10 cells by affecting SP1/AT(1)R DNA binding, thus reducing AT(1)R-mediated vasoconstriction and subsequently prevents the development of hypertension in an Ang II-induced hypertensive model.