Stimulation of a neuroimmune pathway protects from hypertension (860.22)

Vagus nerve stimulation can suppress cytokine release from splenic immune cells and therefore reduce systemic inflammation through a pathway involving nicotinic acetylcholine receptors (α7nAChR). We tested whether activation of this ‘cholinergic anti‐inflammatory pathway’ protects from hypertension during systemic lupus erythematosus (SLE), a chronic autoimmune inflammatory disorder with autonomic dysfunction, renal injury, and hypertension. A female mouse model of SLE that develops hypertension ( NZBWF1 ) was infused with nicotine hydrogen tartrate salt (2 mg/kg/day, subcutaneously) or saline for 7 days via osmotic minipumps. Splenic TNF‐α protein expression was higher in SLE mice (1.37±0.06) than controls (0.44±0.08; p<0.001), nicotine‐treated controls (0.48±0.05; p<0.001), and nicotine‐treated SLE mice (1.09±0.06; p=0.041). Albumin excretion rate (μg/day) was increased in SLE mice compared to controls (157±62 vs. 59±15; p=0.038). Nicotine prevented the rise in albuminuria in SLE mice (112±42; p=0.013), but had no effect in controls (46±8). Blood pressure (mmHg) was increased in SLE mice compared to controls (140±4 vs. 114±2; p<0.001). Nicotine prevented the rise in blood pressure in SLE mice (129±4; p=0.022), but did not alter blood pressure in controls (121±3). These data suggest the anti‐inflammatory effects of nicotine may prevent hypertension in mice with SLE and that the novel cholinergic anti‐inflammatory pathway may be an important target in patients with hypertension associated with chronic inflammatory diseases. Grant Funding Source : Supported by F32HL114272 and P01HL051971