Downregulation of alpha7 nicotinic acetylcholine receptor in two-kidney one-clip hypertensive rats

Abstract

BackgroundInflammation processes are important participants in the pathophysiology of hypertension and cardiovascular diseases. The role of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. Our previous study has demonstrated that the α7nAChR-mediated cholinergic anti-inflammatory pathway is impaired systemically in the genetic model of hypertension. In this work, we investigated the changes of α7nAChR expression in a model of secondary hypertension.MethodsThe 2-kidney 1-clip (2K1C) hypertensive rat model was used. Blood pressure, vagus nerve function, serum tumor necrosis factor-α (TNF-α) and both the mRNA and protein levels of α7nAChR in tissues from heart, kidney and aorta were measured at 4, 8 and 20 weeks after surgery.ResultsCompared with age-matched control, it was found that vagus nerve function was significantly decreased in 2K1C rats with the development of hypertension. Serum levels of TNF-α were greater in 2K1C rats than in age-matched control at 4, 8 and 20 weeks. α7nAChR mRNA in the heart was not altered in 2K1C rats. In the kidney of 2K1C rats, α7nAChR expression was significantly decreased at 8 and 20 weeks, but markedly increased at 4 weeks. α7nAChR mRNA was less in aorta of 2K1C rats than in age-matched control at 4, 8 and 20 weeks. These findings were confirmed at the protein levels of α7nAChR.ConclusionsOur results suggested that secondary hypertension may induce α7nAChR downregulation, and the decreased expression of α7nAChR may contribute to inflammation in 2K1C hypertension.

Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation

“…Vagal efferent suppresses the release of TNF-a via releasing Ach to act on a7nAChR in resident macrophages in the abdominal organs, which includes the liver (Borovikova et al, 2000;Tracey, 2002;Wang et al, 2003). Down-regulation of a7nAChR contributes to the development of end-organ damage by inducing inflammation Chen et al, 2012). In addition to this intrinsic anti-inflammatory characteristic, a7nAChR agonist can also inhibit the severe sepsis related to the chemokine of HMGB1 (Wang et al, 2004).…”

Activation of a7 Nicotinic Acetylcholine Receptor Protects Against Oxidant Stress Damage Through Reducing Vascular Peroxidase-1 in a JNK Signaling-Dependent Manner in Endothelial Cells

“…Our group previously showed that activation of α7nAChR protects against lipopolysaccharide-induced septic shock via inhibiting release of inflammatory cytokines [14]. We also demonstrated that downregulation of α7nAChR might contribute to the development of end organ damage through inducing cardiovascular inflammation in both genetic and experimental hypertension [12,13]. Besides this intrinsic anti-inflammatory characteristic, we hypothesized that there might be more molecular mechanisms underlying the protective effects of α7nAChR in cardiovascular system.…”

“…Recently, α7nAChR has attracted great attention due to its essential role in the cholinergic anti-inflammatory pathway [7,8]. In cardiovascular system, the α7nAChR was reported as an important protector in myocardial ischemia/reperfusion injury [9], stroke [10], atherosclerosis [11] and hypertension [12,13]. Our group previously showed that activation of α7nAChR protects against lipopolysaccharide-induced septic shock via inhibiting release of inflammatory cytokines [14].…”

Dysfunctional Brain-bone Marrow Communication: A Paradigm Shift in the Pathophysiology of Hypertension

“…In another animal model, chronic vascular risk factors have been associated with decreases in cholinergic neurons [68]. Further evidence from a two-kidney one-clip hypertension model suggests that secondary hypertension induces cholinergic receptor down-regulation, which may ultimately contribute to the inflammatory processes [69]. Therefore, the importance of understanding the mechanism of the cholinergic anti-inflammatory pathway in hypertension is becoming increasing evident, and may provide a novel therapeutic target in the treatment of neurogenic hypertension.…”