Key result
The specific creatine kinase inhibitor DNFB significantly reduced vascular contractility to 24.3% of baseline in isolated human resistance arteries, demonstrating a major role for creatine kinase in microvascular contractility.
Why the study?
Does creatine kinase inhibition with DNFB reduce vascular contractility in isolated human resistance arteries from normotensive and hypertensive women?
Does creatine kinase inhibition with DNFB reduce vascular contractility in isolated human resistance arteries from normotensive and hypertensive women?
Absolute Event Rate: 24.3% vs 100%
p-value: p=<0.001
Creatine kinase inhibition significantly reduces microvascular contractility in human resistance arteries, suggesting CK plays a major role in pressor responses and could be a novel target for hypertension.
CK inhibition markedly attenuates resistance artery contractility in non-pregnant women; extends prior pregnancy findings but leaves open therapeutic relevance.
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.
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Taherzadeh et al. (2015) studied Normotension and primary hypertension (n=19). 2,4-dinitro-1-fluorobenzene (DNFB) vs. Baseline was evaluated on Residual vascular contractility compared to baseline (p=<0.001). The specific creatine kinase inhibitor DNFB significantly reduced vascular contractility to 24.3% of baseline in isolated human resistance arteries, demonstrating a major role for creatine kinase in microvascular contractility.
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