Creatine kinase inhibition lowers systemic arterial blood pressure in spontaneously hypertensive rats: a randomized controlled trial. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Journal of hypertension. Volume 34:Issue 12(2016:Dec.)
• Page Start: 2418
• Page End: 2426
• Publication Date: 2016-12
• Subjects: antihypertensive treatment -- beta-guanidinopropionic acid -- blood pressure -- creatine kinase -- drug development -- hypertension -- spontaneously hypertensive rat; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000001090
• Languages: English
• ISSNs: 1473-5598

Abstract

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.