Evidence of an Impaired Neuroimmune Pathway in Autoimmune‐Associated Hypertension

Abstract

The cholinergic anti-inflammatory pathway (CAP) is a novel neuroimmune mechanism that suppresses splenic cytokine release upon stimulation. An impaired CAP would promote chronic inflammation and therefore is implicated in the development of hypertension. An important component of the CAP is the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) in the spleen and we hypothesize that this receptor is altered during hypertension. We measured splenic protein expression of α7nAChR and the vesicular acetylcholine transporter (VAChT) in female mice with systemic lupus erythematosus (SLE), a chronic autoimmune inflammatory disorder with autonomic dysfunction and prevalent hypertension. SLE (NZBWF1) mice had 365±30% higher splenic protein expression of α7nAChR compared to control NZW mice (0.038±0.002 vs. 0.008±0.003; p<0.001). Similarly, splenic protein expression of VAChT was 24.4±7.6% higher in SLE mice compared to controls (0.33±0.02 vs. 0.26±0.03; p=NS). Blood pressure in these SLE mice was 20±2% higher than controls (139±2 vs. 116±2; p<0.01). These data suggest the CAP may be impaired at the level of the α7nAChR in SLE mice and complements previously described data that suggest stimulation of the pathway at the level of the receptor reduces blood pressure in SLE mice. Taken together, the cholinergic anti-inflammatory pathway, particularly the α7nAChR in the spleen, may be an important target in patients with hypertension and other diseases of chronic inflammation. Support: AHA-14SDG18320033