Dear Editor,

We thank Dr. Ferrario and colleagues for their interest in our work. They suggest that we cannot conclude that liver-targeted angiotensinogen (AGT) small interfering (si)RNA lowers brainstem angiotensin (Ang) II levels, and that brain-derived AGT likely contributes to brain Ang II production after all, for instance after AGT siRNA treatment.

We note that the deoxycorticosterone acetate (DOCA)-salt hypertension model is generally believed to involve up-regulation of the brain renin–angiotensin system (RAS), while the circulating RAS is suppressed [1,2]. Although originally this was attributed to up-regulated brain levels of renin and/or prorenin, when quantifying brain renin/prorenin after DOCA-salt, it was actually observed that their levels decreased in parallel with those in blood [3]. Moreover, in absolute terms the brain renin and prorenin levels were excessively low, and at most represented renin and prorenin in trapped blood. Thus, essentially, there is no renin or...

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