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Total and Afferent Renal Denervation Blunts Hypertension and Central and Renal Inflammation in the Developmental Phase of 2‐Kidney, 1‐Clip Hypertension
Author(s) -
Lauar Mariana Ruiz,
Van Helden Dusty,
Banek Christopher T.,
Evans Louise C.,
Menani José Vanderlei,
Osborn John W.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04272
Subject(s) - medicine , renovascular hypertension , denervation , kidney , renal artery , blood pressure , renal artery stenosis , renal ischemia , endocrinology , population , ischemia , cardiology , reperfusion injury , environmental health
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 and an area that also receives input from afferent renal nerves. In the present study, we tested the hypothesis that renal nerves modulate the levels of hypothalamic and renal proinflammatory cytokines and mean arterial pressure (MAP) during the development of 2K1C hypertension in rats. Male Sprague‐Dawley rats (150–180 g, n=5–8/group) were instrumented with telemeters to measure MAP. One week later a clip was placed on the left renal artery of the rats to generate 2K1C HTN. In the same surgery rats also underwent either total or afferent RDN (2K1C‐TRDN or 2K1C‐ARDN) of the clipped kidney. In sham rats (2K1C‐sham) the left renal artery was exposed but not denervated. MAP was continuously measured for the following 6 weeks after which rats were euthanized and brains and kidneys removed for measurement of hypothalamic and renal cytokine content. MAP at the end of the study was 160±6 mmHg in 2K1C‐sham rats. In contrast, MAP was significantly lower in both 2K1C‐TRDN (135±7 mmHg) and 2K1C‐ARDN (133±7 mmHg) rats. TRDN and ARDN statistically reduced hypothalamic protein levels of TNF‐α (0.24±0.01 and 0.2±0.01 pg/mg, respectively) compared to 2K1C‐sham rats (0.3±0.02 pg/mg). Similarly, ARDN statistically reduced hypothalamic IL1β, IL‐2 in 2K1C rats. TRDN trended to the same effect but this was not statistically significant. Renal inflammatory cytokines/chemokines (MCP‐1, IL‐6, TNF‐α) were increased in clipped compared with non‐clipped kidney in 2K1C‐rats. Moreover, ARDN and TRDN statistically reduced this inflammatory response. These results suggest that RDN decreases hypothalamic and renal inflammation in 2K1C hypertensive rats and this may be one mechanism by which RDN decreases MAP in the developmental phase of the 2K‐1C hypertension model. Support or Funding Information NIH R01 HL116476, FAPESP (2018/11221‐1) and PROPE/FUNDUNESP