肌酸激酶抑制可降低自发性高血压大鼠的系统性动脉血压：一项随机对照试验。

Creatine kinase inhibition lowers systemic arterial blood pressure in spontaneously hypertensive rats: a randomized controlled trial.

作者信息

Karamat Fares A, Oudman Inge, Haan Yentl C, van Kuilenburg Andre B P, Leen Rene, Danser Jan A H, Leijten Frank P J, Ris-Stalpers Carrie, van Montfrans Gert A, Clark Joseph F, Brewster Lizzy M

机构信息

aDepartment of Vascular Medicine bLaboratory for Genetic and Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam cDepartment of Vascular Medicine and Pharmacology, Erasmus Medical Center, Rotterdam dDepartment of Obstetrics and Gynaecology and Reproductive Biology Laboratory eDepartment of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands fThe Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, Ohio, USA.

出版信息

J Hypertens. 2016 Dec;34(12):2418-2426. doi: 10.1097/HJH.0000000000001090.

DOI:10.1097/HJH.0000000000001090

PMID:27512977

Abstract

OBJECTIVE

Creatine kinase is reported to be a main predictor of blood pressure (BP) in the general population, with a strong correlation between resistance artery creatine kinase expression and clinical BP in humans. The enzyme rapidly regenerates ATP near cytoplasmic ATPases involved in pressor responses, including resistance artery contractility and renal sodium retention. Therefore, we assessed whether creatine kinase inhibition reduces BP.

METHODS

We implemented the 'Animal Research: Reporting of In Vivo Experiments' guideline. In a 4-week randomized controlled trial, male 16-week-old spontaneously hypertensive rats (N = 16) were randomly assigned to the specific competitive creatine kinase inhibitor beta-guanidinopropionic acid (3%)-supplemented chow vs. standard chow. BP measured by the tail-cuff method was the main outcome. Other outcomes included vasodilation in isolated arteries and renal renin expression.

RESULTS

Creatine kinase inhibition reduced BP safely and reversibly. Mean baseline BP of, respectively, 191.5 (standard error 4.3) mmHg SBP and 143.1 (4.1) mmHg DBP was reduced by, respectively, 42.7 (5.5) mmHg SBP and 35.6 (5.0) mmHg DBP (P < 0.001) compared with controls, with evidence of enhanced vasodilation and a diuretic effect.

CONCLUSION

To our knowledge, this is the first report on the BP-lowering effect of creatine kinase inhibition. Our data indicate that modulation of the creatine kinase system is a potential novel treatment target for hypertension.

摘要

目的

据报道，肌酸激酶是普通人群血压（BP）的主要预测指标，人体阻力动脉肌酸激酶表达与临床血压之间存在强相关性。该酶在参与升压反应（包括阻力动脉收缩性和肾钠潴留）的细胞质ATP酶附近迅速再生ATP。因此，我们评估了抑制肌酸激酶是否能降低血压。

方法

我们遵循了“动物研究：体内实验报告”指南。在一项为期4周的随机对照试验中，将16周龄的雄性自发性高血压大鼠（N = 16）随机分为两组，一组给予添加特定竞争性肌酸激酶抑制剂β-胍基丙酸（3%）的饲料，另一组给予标准饲料。通过尾袖法测量的血压是主要观察指标。其他观察指标包括离体动脉的血管舒张和肾素表达。