Abstract--It has been suggested that the effects of angiotensin II type 1 receptor (AT₁R) blockers are in part because of angiotensin II type 2 receptor (AT₂R) signaling. Interactions between the AT₂R and kinins modulate cardiovascular function. Because AT₂R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT₁R blocker valsartan and the ACE inhibitor benazepril require AT₂R signaling through the bradykinin 1 and 2 receptors (B₁R and B₂R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT₂R inhibitor), valsartan+des-arg⁹-[Leu⁸]-bradykinin (B₁R inhibitor), valsartan+HOE140 (B₂R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT₂R, B₁R, or B₂R in the presence of valsartan prevented the reduction seen with valsartan alone. B₂R blockade inhibited the effect of benazepril. Injury increased AT₁R, AT₂R, B₁R, and B₂R expression. Treatment with valsartan but not benazepril significantly increased intima AT₂R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT₂R, B₁R, and B₂R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT₂R, B₁R, and B₂R. Results suggest that AT₂R expression and increased cGMP represent a molecular mechanism that differentiates AT₁R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.