Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized lowdensity lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (Po0.026 and Po0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (Po0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (Po0.001). oxLDL correlated with MDA positively (P ¼ 0.008), and PON1 negatively (P ¼ 0.008). A negative correlation between MDA and PON1 (P ¼ 0.014) was detected. MDA correlated positively with both SBP and DBP (P ¼ 0.001), while PON1 correlated with both of them negatively (P ¼ 0.01 and P ¼ 0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P ¼ 0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.
The aim of this study was to perform an extensive evaluation of target organ status, metabolic abnormalities and hemodynamic alterations in white coat hypertension (WCH). Fifty normotensive (NT), 90 WCH (ambulatory daytime blood pressure < 135/85 mmHg) and 101 hypertensive (HT) subjects underwent extensive biochemical, echocardiographic, fundoscopic examination. In a subgroup study, arterial compliance and intima-media thickness (IMT) were measured by Doppler ultrasound in left common carotid artery. WCH subjects were found to have higher body mass index (BMI) than the NTs (p = 0.042). Left ventricle mass index (LVMI) was greater in the WCHs than the NTs (p < 0.001), but significantly less than the HTs (p < 0.001). Hypertensive retinopathy was observed in the WCHs, but was less severe and rare compared to the HTs (13% vs 27%). Both WCHs and HTs had high levels of urinary albumin excretion (UAE) (p = not significant). Total cholesterol was higher in WCHs than in the NTs (p = 0.04) The distensibility coefficient (DC) of the WCHs was significantly greater than the HTs (p < 0.01), while significantly smaller than the NTs (p < 0.01). The compliance coefficient (CC) of the WCHs was significantly higher than the HTs (p < 0.01), and significantly less than the NTs (p < 0.01). The IMT in the HTs was significantly higher than the WCHs (0.81 +/- 0.05 vs 0.70 +/- 0.04 mm; p < 0.001) and the NTs (p < 0.001). The difference between the NTs and the WCHs was not significant. Our data indicate that patients with WCH represent an intermediate group between NTs and sustained HTs where target organ damage and cardiovascular risk is concerned.
Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. The aim of this study was to compare the risk conferred by white coat hypertension (WCH) vs sustained hypertension in the development of the endothelial dysfunction and abnormal angiogenesis by evaluating nitric oxide (NO ¼ NO 2 þ NO 3 ), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and E-selectin levels in plasma. The study group included 102 subjects, 34 with WCH (17 male and 17 female patients) aged 49711 years, 34 sustained hypertensives (HT) (15 male and 19 female patients) aged 47711 years and 34 normotensive control subjects (NT) (16 male and 18 female patients) aged 48710 years. WCH was defined as clinical hypertension and daytime ambulatory blood pressure less than 135/85 mmHg. The subjects were matched for age, gender, body mass index and the patients with smoking habit, dyslipidaemia, and diabetes mellitus were excluded from the study. The NO, ET-1, VEGF and E-selectin levels were analysed by ELISA technique. The WCH subjects had significantly higher levels of NO than the HT (41.6872.23 vs 32.1872.68 lmol/l; Po0.001) and significantly lower values than the NT (48.2474.29 lmol/l; Po0.001). ET-1 levels of the WCH group were significantly higher than the NT (8.1070.92 vs 5.9570.26 ng/ml; Po0.001) and significantly lower than the HT (11.4670.59 ng/ml; Po0.001). Considering with VEGF, the WCH group had significantly higher levels than the NT (195.88711.84 vs 146.26718.67 pg/ml; Po0.001), but the difference from the HT group was not significant (203.3577.48 pg/ml; P ¼ 0.062). E-selectin in the WCH group was significantly lower than the HT (4.7770.52 vs 8.4972.85; Po0.001), but the difference from the NT group was not significant (3.8670.67; P ¼ 0.077). Our data demonstrate that WCH is associated with endothelial dysfunction and abnormal angiogenesis. The degree of these changes is not as severe as observed in hypertensive population.
White coat hypertension (WCH) is a high cardiovascular risk condition, and a fundamental understanding of the cause and pathophysiology of the disorder is still lacking. Recent studies demonstrated that microRNAs (miRNAs) are involved in hypertension; however, the roles of miRNAs in WCH are not known.The expressions of selected 10 miRNAs were investigated independently in plasma samples from 30 hypertension (HT) patients, 30 WCH patients, and 30 normotensive (NT) subjects.MiR-21, miR-122, miR-637, and let-7e expression levels were significantly upregulated in the HT group compared with the NT groups (P = 0.017, P = 0.022, P = 0.048, and P = 0.013, respectively). MiR-122 and miR-637 expressions were also significantly upregulated in the WCH group compared with the NT group (P = 0.048 and P = 0.039, respectively). MiR-296-5p expression level was significantly downregulated in HT patients and upregulated in the WCH patients compared with the NT group (P = 0.049 and P = 0.039, respectively).Additionally, the ambulatory 24-hour and daytime systolic and diastolic blood pressures were negatively correlated with miR-296-5p. MiR-296 and miR-637 had area under the curve (AUC) values of 0.778 and 0.774, respectively, which demonstrates their sufficiency to distinguish WCH from NT individuals. MiR-296 and miR-637 had AUC values of 0.868 and 0.680, respectively, which shows their potential to distinguish WCH from HT individuals.We report for the first time a plasma miRNA profile for WCH patients and demonstrate a novel link between miRNA and WCH. These findings may reveal crucial insights into the development of WCH.
Elevated plasma levels of the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) contribute to endothelial dysfunction and seem to be a predictor for cardiovascular mortality. Elevated ADMA plasma concentrations have been demonstrated in patients with hypertension. However, the plasma concentrations of ADMA in white coat hypertension (WCH) has not been previously studied. The aim of this study was to evaluate ADMA in WCH and compare with normotensive (NT) and hypertensive (HT) patients. We also evaluated the relation between ADMA and NO in these three groups. For this purpose, 34 NT, 34 white coat hypertensive (clinical hypertension and ambulatory daytime blood pressure o135/85 mmHg) and 34 HT patients were recruited in this study. The subjects were matched for age, gender, body mass index (BMI) and the patients with smoking habit, dyslipidaemia and diabetes mellitus were excluded. The ADMA levels were determined by high performance liquid chromatography. Plasma ADMA levels were significantly higher in WCH group than in the NT group (3.2170.49 lmol/l vs 2.8470.58 lmol/l, P ¼ 0.046). It was significantly higher in the HT group than in the NTs (4.2470.38 lmol/l, Po0.001). There was also a significant difference between the HT and WCH groups (Po0.001). The WCH subjects had significantly higher levels of NO than the HTs (41.6872.23 vs 32.1872.68 lmol/l; Po0.001) and significantly lower values than the NTs (48.247 4.29 lmol/l; Po0.001). In WCH and HT group, there was a negative correlation between ADMA and NO (r ¼ À0.515, P ¼ 0.003 and r ¼ À0.389, P ¼ 0.034, respectively). In NT subjects, there was no correlation between these two parameters (r ¼ À0.287, P ¼ 0.124). The correlation between ADMA and NO was stronger in WCH group than in HT group. Although NO levels in HT patients were lower than WCHs and ADMA levels were higher in HT patients than WCHs, the negative correlation of these two parameters were more pronounced in WCH group. Decreased NO and increased ADMA levels in WCH may indicate endothelial dysfunction. Our data indicate also that WCH represent an intermediate group between NT and HT when endothelial dysfunction is concerned.
Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.
Ezetimibe therapy has beneficial effects on fibrinolytic activity and homeostasis between oxidant and antioxidant activity in hyperlipidemic patients This may be through lowering lipid levels or other mechanisms such as decreasing insulin resistance and the pleiotropic effects of the drug.
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