Relation of C-Reactive Protein to Oxidative Stress and to Endothelial Activation in Essential Hypertension

Cottone, Santina; Mulè, Giuseppe; Nardi, Emilio; Vadalà, Anna; Guarneri, Marco; Briolotta, Chiara; Arsena, Rosalia; Palermo, Alessandro; Riccobene, Raffaella; Cerasola, Giovanni

doi:10.1016/j.amjhyper.2005.09.005

Cited by 78 publications

(65 citation statements)

References 29 publications

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“…Our finding of elevated plasma levels and renal excretion of HODE in patients with essential hypertension extends prior reports in essential hypertension of increased plasma levels of the ROS markers of hydrogen peroxide (22), plasma protein carbonyl derivatives (19,40), and lipid peroxidation products (9,10,19,28,36,37,38,43), oxidized to reduced ratio of glutathione (26,27,38) and O 2 ⅐ Ϫ in activated polymorphonuclear leukocytes (21,25,37,53). However, other studies have failed to detect an increase in renal excretion of lipid peroxidation products (11) or ROS in lymphocytes (30) in hypertensive subjects.…”

Section: Discussionsupporting

confidence: 77%

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Wang

Strandgaard²,

Iversen³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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-We reported impaired endotheliumderived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n ϭ 9) compared with normal controls (n ϭ 10). We now test the hypothesis that the patients in this study have increased circulating levels of the cNOS inhibitor, asymmetric dimethylarginine (ADMA), or the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (HODE), which is a marker of reactive oxygen species. Patients had significantly (P Ͻ 0.001) elevated (means Ϯ SD) plasma levels of ADMA (P ADMA, 766 Ϯ 217 vs. 393 Ϯ 57 nmol/l) and symmetric dimethylarginine (P SDMA: 644 Ϯ 140 vs. 399 Ϯ 70 nmol/l) but similar levels of L-arginine accompanied by significantly (P Ͻ 0.015) increased rates of renal ADMA excretion (21 Ϯ 9 vs. 14 Ϯ 5 nmol/ mol creatinine) and decreased rates of renal ADMA clearance (18 Ϯ 3 vs. 28 Ϯ 5 ml/min). They had significantly increased plasma levels of HODE (P HODE: 309 Ϯ 30 vs. 226 Ϯ 24 nmol/l) and renal HODE excretion (433 Ϯ 93 vs. 299 Ϯ 67 nmol/mol creatinine). For the combined group of normal and hypertensive subjects, the individual values for plasma levels of ADMA and HODE were both significantly (P Ͻ 0.001) and inversely correlated with microvascular EDRF/NO and positively correlated with mean blood pressure. In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure. blood pressure; 13-hydroxyoctadecadienoic acid; endothelium-derived relaxation factor/nitric oxide; albuminuria MOST OF THE ESTABLISHED AND nontraditional cardiovascular risk factors are associated with endothelial dysfunction (3,5,7,18,45). This includes those with essential hypertension in some (29,33,34,35,39,42,50), but not all, studies (54). Endothelial function depends on the integrity of constitutive nitric oxide synthase (cNOS) and the availability and vascular signaling of its product, nitric oxide (NO). Endothelial dysfunction is of clinical importance since it predisposes to the development of hypertension and atherosclerosis and consequently is a predictor of subsequent adverse cardiovascular events (34).Endothelial dysfunction has been ascribed to two principal factors. One is an enhanced vascular generation of superoxide anion (O 2 ⅐ Ϫ ) that bioinactivates endothelial-derived NO (5), thereby reducing endothelial function and forming peroxynitrite (ONOO Ϫ ). Peroxynitrite itself can nitrosate and inactivate prostacyclin synthase (46), which is an additional pathway mediating endothelium-dependent relaxation. A second factor is generation of asymmetric dimethylarginine (ADMA), which inhibits nitric oxide synthase (6) and inhibits the cellular uptake of L-arginine by the cationic amino acid transporters (CATs) (8).We have studied endothelial function and cNOS activity directly in subcutaneous resistance vessels dissected from glute...

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Section: Discussionsupporting

confidence: 77%

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Wang

Strandgaard²,

Iversen³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…High levels of CRP have been found in diabetes (18) and essential hypertension (19) and, furthermore, have been shown to significantly correlate with both oxidative stress and endothelial activation (20). NAC ϩ ARG treatment has been able to decrease CRP, likely due to both an antioxidant effect and an increased NO availability, which downregulates CRP expression in vivo (21), supporting the hypothesis that strategies meant to lower plasma CRP could include the increase of both NO production and availability.…”

Section: Discussionsupporting

confidence: 48%

Long-Term N-Acetylcysteine and l-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes

et al. 2008

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OBJECTIVE -Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of L-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation. RESEARCH DESIGN AND METHODS-A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC ϩ ARG for 6 months.RESULTS -The NAC ϩ ARG treatment caused a reduction of both systolic (P Ͻ 0.05) and diastolic (P Ͻ 0.05) mean arterial blood pressure, total cholesterol (P Ͻ 0.01), LDL cholesterol (P Ͻ 0.005), oxidized LDL (P Ͻ 0.05), high-sensitive C-reactive protein (P Ͻ 0.05), intracellular adhesion molecule (P Ͻ 0.05), vascular cell adhesion molecule (P Ͻ 0.01), nitrotyrosine (P Ͻ 0.01), fibrinogen (P Ͻ 0.01), and plasminogen activator inhibitor-1 (P Ͻ 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P Ͻ 0.02). HDL cholesterol increased (P Ͻ 0.05). No changes in other parameters studied were observed.CONCLUSIONS -NAC ϩ ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients. Diabetes Care 31:940-944, 2008

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“…The mechanism by which increased oxidative stress and an inflammatory state worsen the grade of sclerotic changes is unknown. Oxidative stress is considered to be involved in endothelial changes [16]. Further examinations including of endothelial function are needed to clarify these points.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress, Inflammation, and Atherosclerotic Changes in Retinal Arteries in the Japanese Population; Results from the Mima Study

et al. 2008

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Abstract. Oxidative stress and inflammation are known to play roles in the pathogenesis of vascular events. The aim of this study was to investigate the relationship between oxidative stress, inflammation, and atherosclerosis in the general population. A population-based, cross-sectional study was made of 282 people (126 men and 156 women, mean age; 65 ± 13, mean BMI; 25.4 ± 2.7 kg/m 2 ) recruited from the Mima study in Tokushima Prefecture. Risk factors included age, sex, body mass index (BMI), cigarette smoking, systolic and diastolic pressure, fasting blood glucose, serum lipids, and high-sensitive C-reactive protein (hs-CRP). Oxidative stress in blood samples was measured by the diacron reactive oxygen metabolites (ROMs) test. The degree of sclerotic change was determined from fundus photographs according to Scheie's classification. After adjustment for age and sex, ROM levels positively correlated with hs-CRP levels, but not with ghrelin, leptin and adiponectin levels. Furthermore, ROM and hs-CRP levels positively and individually correlated with the grade of sclerotic change in the fundus oculi independent of age in a multiple regression analysis. These results suggest that oxidative stress and chronic inflammation promote atherosclerosis in the retinal arteries in the general population.

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Relation of C-Reactive Protein to Oxidative Stress and to Endothelial Activation in Essential Hypertension

Abstract: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.

Cited by 78 publications

References 29 publications

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Long-Term N-Acetylcysteine and l-Arginine Administration Reduces Endothelial Activation and Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes

Oxidative Stress, Inflammation, and Atherosclerotic Changes in Retinal Arteries in the Japanese Population; Results from the Mima Study

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