Dear Editor

We read with great interest the article by Uijl et al. [1] who reported that liver-directed small interfering RNA (siRNA) targeted to angiotensinogen (AGT) does not reverse the hypertension induced in male Sprague–Dawley rats by the implant of a deoxycorticosterone acetate (DOCA) pellet and 9.0% saline in lieu of tapwater. In the elegantly conducted experiments, a 97% suppression of circulating AGT in siRNA-treated rats doubled brainstem AGT mRNA while having no effect on corresponding brain tissue AGT concentrations. While we consider the presented results important, we do highlight concerns limiting the correct interpretation of the published data. First, Uijl et al. [1] detailed analysis of the changes in circulating and tissue angiotensins over interprets the data reported for brainstem Ang II concentrations between DOCA+salt vehicle and siRNA DOCA+salt treated rats. The data illustrated in their Figure 4 (Panel B) show that brainstem Ang II...

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