AT₂R and Sympathetic Outflow

Angiotensin type 2 receptor (AT₂R) protein content has been demonstrated in the sympathetic regulatory regions of the brain in mature rats and mice. In the rostral ventrolateral medulla of normal animals, the AT₂R tonically suppresses sympathetic tone by increasing presympathetic neuronal potassium current and therefore reducing neuronal excitability and discharge. In the chronic heart failure (CHF) state and in neurogenic hypertension, central AT₂R expression is significantly downregulated. This pathological alteration of AT₂R signaling contributes to sympathetic hyperactivity, a major characteristic of these two diseases. Gene transfer-induced overexpression and pharmacologically evoked activation of central AT₂Rs provide a potential therapeutic strategy in the CHF and hypertension states by promoting sympathetic inhibition.