Uijl E, et al. - Because long-lasting antihypertensive effects may be provided by small interfering RNAs (siRNAs) targeting hepatic angiotensinogen (Agt), researchers used spontaneously hypertensive rats to evaluate the effectiveness of a novel AGT siRNA. They treated rats with vehicle, siRNA (10 mg/kg fortnightly; subcutaneous), valsartan (31 mg/kg per day; oral), captopril (100 mg/kg per day; oral), valsartan+siRNA, or captopril+valsartan for 4 weeks (all groups, n=8). According to findings, > 99% suppression of circulating AGT is needed for Ang II elimination. The greatest attenuation in blood pressure and cardiac hypertrophy was induced by maximal blockade of the renin-angiotensin system achieved with valsartan+siRNA; the efficacy of AGT lowering alone was equivalent to that of conventional renin-angiotensin system inhibitors. Given its stable and sustained efficacy, lasting weeks, the possible utility of RNA interference in improving therapy adherence and treating hypertension was suggested.