Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Circ J. 2010 Nov;74(12):2622-6. doi: 10.1253/circj.cj-10-0427. Epub 2010 Oct 9.
Experimental animal data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) might reduce enhanced sympathetic activity, a hallmark of hypertensive patients. This hypothesis was tested for the first time in patients with primary hypertension.
Using a prospective, randomized, placebo-controlled, double-blind, cross-over design, a proof-of-principle trial was performed in 13 patients with mild to moderate primary hypertension, who were randomly assigned to a regimen of atorvastatin (80mg/day) for 3 weeks, followed by placebo for 3 weeks or to a regimen of placebo for 3 weeks, followed by atorvastatin (80mg/day) for 3 weeks. Microneurography was used at the end of each treatment period to measure sympathetic nervous system activity (muscle sympathetic nerve activity: MSNA). Heart rate variability (HRV) and plasma norepinephrine concentrations were also measured. Additionally, effects on blood pressure (BP) and heart rate (HR) were assessed by 24-h ambulatory BP measurement. Atorvastatin reduced postganglionic MSNA (atorvastatin 35.0±2.0 vs placebo: 39.2±1.5 bursts/min, P=0.008) and heart frequency corrected MSNA (atorvastatin: 58.5±2.0 vs placebo: 64.7±3.0 bursts/100 beats, P=0.02). Atorvastatin had no significant effect on plasma norepinephrine levels, HRV, BP or HR.
In patients with mild to moderate hypertension, atorvastatin reduces postganglionic MSNA, which supports the hypothesis that HMG-CoA reductase plays a role in sympathetic nervous system activity.
实验动物数据表明,3-羟基-3-甲基戊二酰辅酶 A(HMG-CoA)还原酶抑制剂(他汀类药物)可能降低高血压患者增强的交感神经活性,这是高血压患者的一个标志。这一假设首次在原发性高血压患者中得到了检验。
采用前瞻性、随机、安慰剂对照、双盲、交叉设计,对 13 例轻中度原发性高血压患者进行了一项原理验证试验,患者被随机分为阿托伐他汀(80mg/天)治疗 3 周,随后安慰剂治疗 3 周或安慰剂治疗 3 周,随后阿托伐他汀(80mg/天)治疗 3 周。在每个治疗期结束时使用微神经记录法测量交感神经系统活动(肌肉交感神经活动:MSNA)。还测量了心率变异性(HRV)和血浆去甲肾上腺素浓度。此外,通过 24 小时动态血压测量评估对血压(BP)和心率(HR)的影响。阿托伐他汀降低了节后 MSNA(阿托伐他汀 35.0±2.0 比安慰剂:39.2±1.5 次/分钟,P=0.008)和心率校正后的 MSNA(阿托伐他汀:58.5±2.0 比安慰剂:64.7±3.0 次/100 次心跳,P=0.02)。阿托伐他汀对血浆去甲肾上腺素水平、HRV、BP 或 HR 没有显著影响。
在轻中度高血压患者中,阿托伐他汀降低了节后 MSNA,这支持了 HMG-CoA 还原酶在交感神经系统活性中起作用的假设。