engleski

RELATIONSHIP AMONG OXIDATIVE STRESS, VASCULAR REACTIVITY CHANGES AND BLOOD PRESSURE IN HYPERTENSIVE PATIENTS ON AT1R ANTAGONIST THERAPY

OBJECTIVE: The aim of this study was to assess the effects of AT1-receptor antagonisms on the markers of oxidative stress and endothelial activation in relation to vascular function and arterial blood pressure (ABP) changes in hypertensive patients. DESIGN AND METHODS:30 newly discovered hypertensive subjects of both sexes received AT1 antagonist (olmesartan, 10-20mg/day) during 8 weeks. At the beginning and 8 weeks after therapy flow-mediated dilation (FMD) of brachial artery (BA) was measured by ultrasound (Acuson Siemens X300 ; ultrasound probe VF10-5 ; 105 MHz). The BA diameter, relative change in the diameter (delta r) and percentage of diameter change (FMD%) were calculated for pre-occlusion, and after occlusion duration for 1, 2 and 3min. Serum levels of 8-iso- prostaglendin F2-alpha (8iPGF2α), endoglin and sICAM-1, sVCAM-1 and E-selectin were assessed by commercial ELISA kits. Paired t-test, or t-test were used as appropriate, with Pearson’s correlation calculated ; p<0.05 was significant (SigmaPlotv.11). RESULTS: Eight weeks after therapy, ABP was significantly reduced (≤139/89mmHg ; p<0.001). sICAM-1 and sVCAM-1 levels were significantly decreased and positively correlated to BP whereas sE-selectin was increased and negatively correlated to BP. Although 8iPGF2α and endoglin levels did not significantly change, there was significant positive correlation between 8iPGF2α and diastolic BP (p=0.0383), as well as between endoglin and 8iPGF2α (p=0.0477). The BA diameter was significantly bigger at all measured points compared to pre-therapy values ; delta r was significantly reduced after 3min, and FMD% after 2 and 3min of occlusion. Delta r positively correlated to systolic (SBP) and diastolic (DBP) after 2 and 3 min. FMD% positively correlated to SBP after 3min, and to DBP after 2min of occlusion. 8iPGF2α positively correlated to FMD% after 1 and 2 min occlusion duration ; and to delta r after 1min of occlusion. CONCLUSIONS: Blood vessels were relaxed after therapy due to decreased BP leading to less vigorous FMD response. Level of oxidative stress affected FMD. Endoglin might be a new marker of endothelial dysfunction in systemic hypertension, related to the level of oxidative stress and AT1 receptors' function. Results suggest permissive role of AT1 receptors in maintaining normal vascular function despite BP normalization.

AT-1 receptor blocker; oxidative stress; blood pressure; vascular reactivity; hypertension

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