Recent trials have demonstrated the efficacy and safety of percutaneous renal sympathetic denervation (RDN) for blood pressure (BP)-lowering in patients with uncontrolled hypertension. Nevertheless, major challenges exist, such as the wide variation of BP-lowering responses following RDN (from strong response to no response) and lack of feasible and reproducible peri-procedural predictors for patient response. Both animal and human studies have demonstrated different patterns of BP responses following renal nerve stimulation (RNS), possibly related to varied regional proportions of sympathetic and parasympathetic nerve tissues along the renal arteries. Animal studies of RNS have shown that rapid electrical stimulation of the renal arteries caused renal artery vasoconstriction and increased norepinephrine secretion with a concomitant increase in BP, and the responses were attenuated after RDN. Moreover, selective RDN at sites with strong RNS-induced BP increases led to a more efficient BP-lowering effect. In human, when RNS was performed before and after RDN, blunted changes in RNS-induced BP responses were noted after RDN. The systolic BP response induced by RNS before RDN and blunted systolic BP response to RNS after RDN, at the site with maximal RNS-induced systolic BP response before RDN, both correlated with the 24-h ambulatory BP reductions 3-12 months following RDN. In summary, RNS-induced BP changes, before and after RDN, could be used to assess the immediate effect of RDN and predict BP reductions months following RDN. More comprehensive, large-scale and long term trials are needed to verify these findings.