Fares A Karamat1, Inge Oudman, Yentl C Haan, Andre B P van Kuilenburg, Rene Leen, Jan A H Danser, Frank P J Leijten, Carrie Ris-Stalpers, Gert A van Montfrans, Joseph F Clark, Lizzy M Brewster. 1. 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.
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.
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 hypertensiverats (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.
Authors: Lizzy M Brewster; Inge Oudman; Rani V Nannan Panday; Inna Khoyska; Yentl C Haan; Fares A Karamat; Joseph F Clark; Gert A van Montfrans Journal: J Clin Hypertens (Greenwich) Date: 2018-01-22 Impact factor: 3.738
Authors: Fares A Karamat; Deborah L Horjus; Yentl C Haan; Lisa van der Woude; Marianne C Schaap; Inge Oudman; Gert A van Montfrans; Rienk Nieuwland; Gajja S Salomons; Joseph F Clark; Lizzy M Brewster Journal: Br J Clin Pharmacol Date: 2017-09-20 Impact factor: 4.335
Authors: Adrian Post; Daan Kremer; J Casper Swarte; Sara Sokooti; Fabian A Vogelpohl; Dion Groothof; Ido P Kema; Erwin Garcia; Margery A Connelly; Theo Wallimann; Robin P F Dullaart; Casper F M Franssen; Stephan J L Bakker Journal: J Hypertens Date: 2022-02-01 Impact factor: 4.844