Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
BMC Cardiovasc Disord. 2012 Jun 8;12:38. doi: 10.1186/1471-2261-12-38.
Inflammation 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.
The 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.
Compared 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.
Our results suggested that secondary hypertension may induce α7nAChR downregulation, and the decreased expression of α7nAChR may contribute to inflammation in 2K1C hypertension.
炎症过程是高血压和心血管疾病病理生理学的重要参与者。α7 烟碱型乙酰胆碱受体（α7nAChR）在炎症中的作用最近已被确定。我们之前的研究表明，在高血压的遗传模型中，α7nAChR 介导的胆碱能抗炎途径在全身受到损害。在这项工作中，我们研究了继发性高血压模型中 α7nAChR 表达的变化。
使用 2 肾 1 夹（2K1C）高血压大鼠模型。在手术后 4、8 和 20 周时测量血压、迷走神经功能、血清肿瘤坏死因子-α（TNF-α）以及心脏、肾脏和主动脉组织中 α7nAChR 的 mRNA 和蛋白水平。
与年龄匹配的对照组相比，随着高血压的发展，发现 2K1C 大鼠的迷走神经功能明显降低。与年龄匹配的对照组相比，2K1C 大鼠在 4、8 和 20 周时血清 TNF-α水平更高。2K1C 大鼠心脏中的 α7nAChR mRNA 没有改变。在 2K1C 大鼠的肾脏中，α7nAChR 表达在 8 周和 20 周时显著降低，但在 4 周时显著增加。与年龄匹配的对照组相比，2K1C 大鼠的主动脉中 α7nAChR mRNA 在 4、8 和 20 周时较少。这些发现在 α7nAChR 的蛋白水平上得到了证实。
我们的结果表明，继发性高血压可能会诱导 α7nAChR 下调，α7nAChR 的表达减少可能导致 2K1C 高血压中的炎症。
