LAUSR

&NA; Extracellular sulfatases, sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling and carcinogenesis. Chemokine CCL5 inhibits Ang II‐induced hypertensive mediators via angiotensin II (Ang II) type 2 receptor (AT2 R) pathway in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). In this study, we investigated the effect of Sulfs on anti‐hypertensive effects of CCL5 in SHR VSMCs. CCL5 attenuated Ang II‐induced inhibition of sulfatase activity in SHR VSMCs. Inhibition of Ang II‐induced 12‐lipoxygenase (12‐LO) and endothelin‐1 (ET‐1) expression by CCL5 was reduced in Sulf1 small interfering RNA (siRNA)‐transfected SHR VSMCs. In addition, attenuation of Ang II‐induced dimethylarginine dimethylaminohydrolase‐1 (DDAH‐1) inhibition by CCL5 was reduced in Sulf1 siRNA‐transfected SHR VSMCs. Downregulation of Sulf2 did not affect inhibitory effects of CCL5 on Ang II‐induced 12‐LO and ET‐1 expression and Ang II‐induced inhibition of DDAH‐1 expression in SHR VSMCs. Downregulation of Sulf1 abrogated the expression of CCL5‐induced AT2 R messenger RNA (mRNA) and synergistic effect of CCL5 on Ang II‐induced AT2 R expression in SHR VSMCs. These findings suggest that Sulf1 is a potential up‐regulatory factor in anti‐hypertensive actions of CCL5 via AT2 R pathway on Ang II‐induced hypertensive effects in SHR VSMCs.