Renal Denervation Prevents Nicotine‐Induced Hypertension and Reduces Renal IL‐17a

Interaction between the nervous and immune systems has become a major focus in the pathophysiology of essential hypertension. Cholinergic activation of nicotinic acetylcholine receptors are known to exert an anti‐inflammatory effect. However, we recently demonstrated that in vivo cholinergic activation with nicotine induces renal inflammation and premature development of hypertension in young Spontaneously Hypertensive Rat (SHR). We hypothesized that renal nerves contribute to nicotine‐induced renal inflammation and premature hypertension in young SHR. Following bilateral renal nerve denervation (RND) (or Sham surgery) in young (3–5 week old SHR), we continuously infused nicotine bitartrate (15mg/kg/day) or saline subcutaneously for 2 weeks. Systolic blood pressure was measured by tail cuff. Norepinephrine (NE) and IL‐17a were measured in kidneys by ELISA and Luminex assay, respectively. RND prevented the development of hypertension in response to nicotine infusion in young SHR (n=6), compared to nicotine‐infused Sham operated young SHR (n=3) (140 ± 4 vs 180 ± 5 mmHg, respectively, p<0.001). RND also significantly decreased IL‐17a in kidneys nicotine‐infused SHR, compared with kidneys from sham operated SHR (12 ± 0.7 pg/mL vs 17 ± 0.9 pg/mL, p<0.01). NE analysis of renal tissues confirmed renal denervation with over an 85% reduction in renal NE levels, compared to sham operation (31±11 ng/mg vs 225±43 ng/mg, P<0.05). We conclude that renal nerves mediate nicotine‐induced renal inflammation and hypertension. Support or Funding Information University of Iowa, Carver College of Medicine NIH/NHLBI‐HL119588‐01A1 and HL014388‐48