The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries

Taherzadeh, Z. and Karamat, F. A. and Ankum, W. M. and Clark, J. F. and Van Montfrans, G. A. and Van Bavel, E. and Brewster, L. M. (2016) The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries. American Journal of Hypertension, 29 (2). pp. 170-177.

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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. METHODS AND 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. CONCLUSION 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. © American Journal of Hypertension, Ltd 2015.

Item Type: Article
Additional Information: Cited By :8 Export Date: 16 February 2020 CODEN: AJHYE Correspondence Address: Karamat, F.A.; Department of Vascular Medicine, Academic Medical Center, University of AmsterdamNetherlands; email: F.A.Karamat@amc.uva.nl
Uncontrolled Keywords: blood pressure creatine kinase hypertension resistance artery vasoconstriction 1 fluoro 2,4 dinitrobenzene beta adrenergic receptor blocking agent calcium channel blocking agent dipeptidyl carboxypeptidase inhibitor nitroprusside sodium thiazide diuretic agent adult arterial pressure artery constriction artery diameter Article clinical article controlled study diastolic blood pressure drug effect enzyme inhibition enzyme inhibitor interaction enzyme specificity female human human tissue maternal hypertension microvasculature muscle strength myography prediction pregnancy priority journal resistance blood vessel smooth muscle contractility systolic blood pressure antagonists and inhibitors artery in vitro study metabolism middle aged physiology Arteries Dinitrofluorobenzene Humans In Vitro Techniques
Subjects: QT physiology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 26 Feb 2020 07:47
Last Modified: 26 Feb 2020 07:47
URI: http://eprints.mums.ac.ir/id/eprint/13227

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