The disappearance of brain Ang II combined with a lack of a blood pressure–lowering effect after AGT siRNA raises doubt about the concept of selective brain RAS upregulation in the DOCA-salt model (involving local AGT synthesis in the brain) as the cause of hypertension, also because the amount of renin in brain tissue is low and at most represents circulating renin in trapped blood.41 A more simple explanation is that brain Ang II is taken up from blood.42 Interestingly, despite the absence of a blood pressure–lowering effect, AGT siRNA did reduce cardiac hypertrophy in the DOCA-salt rat. This evidence concerns the gene REN and hypertensive disorder.