Figure 1.

Interaction between afferent renal nerves and renal sympathetic nerve activity in healthy and injured kidneys. (A) In healthy kidneys, increased renal sympathetic nerve activity (RSNA) leads to an activation of α1-adrenoceptors expressed in the renal pelvis, which increases afferent renal nerve activity (ARNA). Subsequently, inhibitory neurons within the brainstem and hypothalamus decrease RSNA via a negative feedback mechanism leading to natriuresis. (B) In hypertension or kidney injury, accumulation of pro-inflammatory cytokines, uremic toxins, or ischemic metabolites activate afferent renal nerves. Under these conditions, the negative feedback mechanism is dysregulated and increased ARNA results in a further activation of renal sympathetic nerves causing the progression of hypertension and hypertensive kidney disease.