Although there are multiple shortcomings of the early AGT ASO drugs, there is accumulating evidence that (i) inhibition of AGT synthesis in brain by ASOs effectively reduces blood pressure in multiple hypertensive rat models, and (ii) this reduction in blood pressure is associated with changes in brain, but not plasma, AngII production, implicating local-specific effects of AngII in hypertension. The gene discussed is AGT; the disease is hypertensive disorder.