Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, Leeds, UK.
J Hypertens. 2010 Oct;28(10):2084-93. doi: 10.1097/HJH.0b013e32833c8a36.
Sympathetic nerve hyperactivity has been associated with hypertension and heart failure and their cardiovascular complications. The α2-adrenergic receptors have been proposed to play a prominent role in the control of sympathetic neural output, and their malfunction to constitute a potential central mechanism for sympathetic hyperactivity of essential hypertension. Reports on the relationship between variant alleles of α2-adrenergic receptor subtypes and sympathetic drive or its effects, however, have not been consistent. Therefore, this study was planned to test the hypothesis that variant alleles of subtypes of α2-adrenergic receptors are associated with raised muscle sympathetic nerve activity (MSNA) in man.
One hundred and seventy-two individuals, with a wide range of arterial pressure, were prospectively examined. Resting MSNA was quantified from multiunit bursts and from single units, and α2-adrenergic receptor subtypes were genotyped from DNA extracted from leucocytes and quantified by spectrophotometry.
No significant relationships between variant alleles of any of the α2A, α2B or α2C subtypes and raised muscle sympathetic activity were found. In contrast, MSNA showed a marked significant curvilinear relationship with age and systolic pressure; sex had a small but statistically significant effect. The α2-adrenergic receptor variants had a similar frequency when hypertensive and normotensive individuals were compared.
Variant alleles of three α2-adrenergic receptor subtypes were not related to resting muscle sympathetic nerve hyperactivity, indicating that their functional differences shown in vitro are not reflected in sympathetic activity in man. Age had a marked effect likely influencing arterial pressure through sympathetic activity.
交感神经活性与高血压和心力衰竭及其心血管并发症有关。α2-肾上腺素能受体被认为在控制交感神经输出中起重要作用，其功能障碍构成了原发性高血压交感神经活性增强的潜在中枢机制。然而，关于 α2-肾上腺素能受体亚型的变异等位基因与交感驱动或其效应之间的关系的报告并不一致。因此，本研究旨在检验这样一个假设，即 α2-肾上腺素能受体亚型的变异等位基因与人类肌肉交感神经活动（MSNA）升高有关。
172 名个体，动脉压范围广泛，前瞻性检查。从多单位爆发和单个单位量化静息 MSNA，并从白细胞提取的 DNA 中进行基因分型，并通过分光光度法进行定量。
未发现任何 α2A、α2B 或 α2C 亚型的变异等位基因与升高的肌肉交感活性之间存在显著关系。相反，MSNA 与年龄和收缩压呈显著的曲线关系；性别有较小但有统计学意义的影响。与高血压和正常血压个体相比，α2-肾上腺素能受体变体的频率相似。
三种 α2-肾上腺素能受体亚型的变异等位基因与静息肌肉交感神经活性升高无关，表明其在体外表现出的功能差异并未反映在人类的交感活性中。年龄的影响明显，可能通过交感神经活性影响动脉压。
