Hypertension (HTN) is a multifactorial disease that affects one third of the population of western countries. Although 95% of cases are of unknown origin (i.e., primary HTN), it is well established that renal ischemia results in secondary renovascular HTN. Experimental renovascular HTN is induced in rats by placing a silver clip on the left renal artery creating a stenosis, which decreases renal perfusion pressure and increases renin release from the clipped kidney (2K1C‐HTN). Previous studies indicate a role of renal nerves in 2K1C‐HTN since renal denervation (RDN) attenuates HTN in 2K1C‐rats. Moreover, activation of the sympathetic nervous system in this model is associated with inflammation in the hypothalamus, a key site for regulation of sympathetic activity that also receives input from afferent renal nerves. In the present study, we tested the hypothesis that renal nerves modulate the levels of hypothalamic proinflammatory cytokines and mean arterial pressure (MAP) in 2K1C rats. Male Sprague‐Dawley rats (150–180 g, n=2–4/group) received a clip on the left renal artery to generate 2K1C HTN and were instrumented with telemeters to measure MAP. Four weeks later rats underwent RDN (2K1C‐RDN) or sham (2K1C‐sham) surgery of the clipped kidney and MAP measurement continued for the following 2 weeks. Rats were then euthanized and brains quickly removed for subsequent measurement of hypothalamic cytokine content. Preliminary data demonstrated that MAP was lower 2K1C‐RDN (157±20 mmHg) than 2K1C‐sham (175±7 mmHg) rats. RDN also tended to decrease hypothalamic cytokine content. IL‐1β was 25±3 pg/mg in 2K1C‐RDN compared to 151±66 pg/mg in 2K1C‐sham rats. IL‐6 content was 24±19 pg/mg in 2K1C‐RDN vs. 39±0.5 pg/mg in 2K1C‐sham rats. The results suggest that RDN may decrease hypothalamic inflammation in 2K1C hypertensive rats and this may be one mechanism by which RDN decreases MAP in this model.Support or Funding InformationFAPESP (2018/11221‐1), PROPE/FUNDUNESP and NIH R01 HL116476.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.