title: The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries.
abstract: BACKGROUND
  Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human hypertension are lacking. Therefore, we further explored CK-dependency of vascular contractility outside the context of pregnancy in normotensive and hypertensive women.
  
  
  RESULTS
  Nineteen consecutive women, mean age 42 years (SE 1.3), mean systolic/diastolic blood pressure respectively 142.6 (SE 5.9)/85.6 (3.4) mm Hg (9 hypertensive), donated an omental fat sample during abdominal surgery. We compared vasodilation after the specific CK inhibitor 2,4-dinitro-1-fluorobenzene (DNFB; 10(-6) mol/l) to sodium nitroprusside (10(-6) mol/l) in isolated resistance arteries using a wire myograph. Additionally, we assessed predictors of vasoconstrictive force. DNFB reduced vascular contractility to 24.3% (SE 4.4), P < 0.001, compared to baseline. Sodium nitroprusside reduced contractility to 89.8% (SE 2.3). Maximum contractile force correlated with DNFB effect as a measure of CK (r = 0.8), and with vessel diameter (r = 0.7). The increase in contractile force was 16.5 mN [9.1-23.9] per unit DNFB effect in univariable and 10.35 mN [2.10-18.60] in multivariable regression analysis.
  
  
  CONCLUSIONS
  This study extends on our previous findings in pregnant normotensive women of CK-dependent microvascular contractility, indicating that CK contributes significantly to resistance artery contractility across human normotension and primary hypertension outside the context of pregnancy. Further studies should explore the effect of CK inhibitors on clinical blood pressure.
authors.affiliation: Neurogenic Inflammation Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Zhila
authors.initials: Z
authors.lastname: Taherzadeh
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; F.A.Karamat@amc.uva.nl.
authors.forename: Fares A
authors.initials: FA
authors.lastname: Karamat
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Willem M
authors.initials: WM
authors.lastname: Ankum
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA;
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Clark
authors.affiliation: Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Gert A
authors.initials: GA
authors.lastname: van Montfrans
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Ed
authors.initials: E
authors.lastname: van Bavel
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Social Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lizzy M
authors.initials: LM
authors.lastname: Brewster
mesh_terms: D000328:Adult; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004139:Dinitrofluorobenzene; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged
chemical_list: D004139:Dinitrofluorobenzene; D003402:Creatine Kinase
keywords: blood pressure; creatine kinase; hypertension; resistance artery; vasoconstriction.