In the frame of this proposal investigators will test the hypothesis that high normal blood pressure (prehypertension; PreHT) induces systemic endothelial dysfunction and endothelial activation in both micro- and macrocirculation, reduces re-endothelialization potential of human endothelial progenitor cells (EPCs) and increases the level of endothelial extracellular vesicles (EVs), which are accompanied by increased oxidative stress level. Furthermore, initial vascular and left ventricle (LV) remodeling contributes to changes in systemic hemodynamics and may be influenced by altered regulatory role of renin-angiotensin system (RAS) and autonomic nervous system (ANS) in PreHT but otherwise healthy individuals. To distinguish high normal blood pressure effect from those considered normal or high, study will be performed in three groups of individuals: prehypertensive (BP 130-139/85-89 mmHg), hypertensive (stage I, BP 140-150/90-100 mmHg), and controls (BP less than or equal to 129/85 mmHg). Altogether, the impairment of normal vascular relaxation mechanisms, endothelial activation as well as vascular and LV remodeling could play crucial role in increased cardiovascular risk and CVDs incidence in PreHT individuals. Moreover, the prognostic significance of assessing endotehlial dysfunction in hypertension (as well as in PreHT) is yet to be established.
Study Type
OBSERVATIONAL
Enrollment
90
Faculty of Medicine Osijek
Osijek, Croatia
Systemic microvascular function
Skin microvascular reactivity assessed by Laser Doppler flowmetry (post-occlusive reactive hyperemia, iontophoresis of acetylcholine and sodium nitroprusside, local thermal hyperemia) - measured in perfusion units (PU)
Time frame: Day 1
Systemic macrovascular function
Vascular ultrasound measurement of brachial artery flow mediated dilation (FMD)
Time frame: Day 1
Aortic stiffness
Measurement of pulse wave velocity (PWV) using impedance cardiography.
Time frame: Day 1
Left ventricle global longitudinal strain
Global longitudinal strain (GLS) of left ventricle obtained by two-dimensional speckle tracking echocardiography.
Time frame: Day 1
Oxidative stress - 8-iso-prostaglandin F2α (8-iso-PGF2α)
ELISA measurement of serum 8-iso-PGF2α concentration. 8-iso-PGF2α is an isoprostane that is produced by the non-enzymatic peroxidation of arachidonic acid in membrane phospholipids.
Time frame: Day 1
Activity of renin-angiotensin system (RAS)
ELISA measurement of plasma renin activity (PRA).
Time frame: Day 1
Endothelial progenitor cells (EPCs)
Detection of EPCs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).
Time frame: Day 1
Endothelial extracellular vesicles (eEVs)
Detection of eEVs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).
Time frame: Day 1
Systemic peripheral vascular resistance
Systemic peripheral vascular resistance assessement using non-invasive impedance cardiography (ICG).
Time frame: Day 1
Autonomic nervous system (ANS) activity
Assessment of a 5-minute heart rate variability (5-min HRV).
Time frame: Day 1
Matrix metalloproteinase 9
ELISA measurement of serum matrix metalloproteinase 9 level.
Time frame: Day 1
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