8-hydroxy-2--deoxyguanosine and Hypertension

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Arginine; Biomarkers; Deoxyguanosine; Dinoprost; Glycation End Products, Advanced; Humans; Hypertension; Lipid Peroxides; Lipoproteins, LDL; Lysine; Oxidative Stress

The association of short-term air pollution filtration with cardiovascular health has been documented. However, the effect of long-term indoor air conditioner filtration on the association between air pollution and cardiovascular health is still unclear. We recruited 200 homemakers from Taipei and randomly assigned 100 of them to air filtration or control intervention; six home visits were conducted per year from 2013 to 2014. The participants under air filtration intervention during 2013 were reassigned to control intervention in 2014. The air pollution measurements consisted of particulate matter less than or equal to 2.5μm in diameter (PM

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Air Conditioning; Air Pollutants; Air Pollution, Indoor; Biomarkers; C-Reactive Protein; Cross-Over Studies; Deoxyguanosine; Female; Fibrinogen; Filtration; Humans; Hypertension; Inflammation; Male; Middle Aged; Oxidative Stress; Particulate Matter; Volatile Organic Compounds

The aim of the present study was to compare the effects of the aldosterone blocker eplerenone and thiazide-like diuretic indapamide on blood pressure (BP) and target organs with reference to salt intake in hypertensive outpatients. Twenty hypertensive patients (nine women and 11 men, mean age 71 ± 13 years) with inadequate BP control despite taking calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were administered eplerenone (50 mg/day) or indapamide (1 mg/day) for 3 months each in a randomized crossover manner. Salt intake, BP and indices of organ damage were assessed at baseline and at the end of each treatment period. Eplerenone and indapamide were similarly effective in lowering office and home BPs. Both the treatments significantly reduced the estimated glomerular filtration rate (eGFR) and increased serum uric acid levels. The treatment with eplerenone significantly increased serum potassium levels, whereas the treatment with indapamide significantly decreased them. The treatment with eplerenone significantly decreased pulse wave velocity and urinary 8-hydroxydeoxyguanosine levels. These changes were not significantly affected by the treatment with indapamide. In conclusion, eplerenone and indapamide were similarly effective in lowering office and home BPs in hypertensive patients treated with CCBs and ARBs. Eplerenone may exert more favorable effects on arterial stiffness and oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Blood Pressure; Blood Pressure Determination; Calcium Channel Blockers; Deoxyguanosine; Diuretics; Eplerenone; Female; Glomerular Filtration Rate; Humans; Hypertension; Indapamide; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Potassium; Pulse Wave Analysis; Spironolactone; Treatment Outcome; Uric Acid

Autosomal dominant polycystic kidney disease (ADPKD) progresses more quickly to end-stage renal disease in patients with hypertension than in their normotensive counterparts. The authors investigated the effect of telmisartan versus enalapril on systolic and diastolic blood pressure (SBP and DBP), urinary albumin excretion (UAE), serum high mobility group box-1 protein (HMGB1), serum interleukin (IL)-6 and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with hypertensive ADPKD.. Twenty patients with hypertensive ADPKD with good renal function were randomly assigned to 1 of 2 treatments: telmisartan 80 mg once daily (n = 10) or enalapril 10 mg once daily (n = 10). Treatment lasted 12 months. SBP, DBP, serum creatinine, UAE, HMGB1, IL-6 and urinary 8-OHdG levels were measured before and 6 and 12 months after treatment.. Both SBP and DBP were significantly reduced after treatment (P < 0.001) in both groups. Serum creatinine changed little during the experimental period in either group. UAE, serum HMGB1, serum IL-6 and urinary 8-OHdG levels were significantly decreased after treatment (UAE, HMGB1 and IL-6, P < 0.001; and 8-OHdG, P < 0.01 versus baseline levels) in both groups. However, the decreases in UAE, serum HMGB1 and serum IL-6 were significantly greater in the telmisartan group than in the enalapril group at 6 months (P < 0.05, P < 0.01 and P < 0.01, respectively) and 12 months (all, P < 0.05).. Telmisartan seems to be equivalent to enalapril in lowering BP, but telmisartan has more potent renoprotective, anti-inflammatory and antioxidative effects than enalapril in patients with hypertensive ADPKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Biomarkers; Creatinine; Deoxyguanosine; Enalapril; Female; HMGB1 Protein; Humans; Hypertension; Inflammation; Interleukin-6; Male; Middle Aged; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Telmisartan

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2'-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Albuminuria; Amlodipine; Antihypertensive Agents; Antioxidants; Blood Pressure; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Fatty Acid-Binding Proteins; Female; Heart Rate; Humans; Hypertension; Incidence; Male; Middle Aged; Oxidative Stress; Prospective Studies; Renal Insufficiency, Chronic

Angiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress in patients without arteriosclerosis. This study aimed to evaluate (1) whether an ARB (candesartan) decreases values for inflammatory parameters in hypertensive patients with type 2 diabetes mellitus of long duration accompanied by arteriosclerosis and (2) whether there any predictors of which patients would receive the benefits of organ protection by candesartan.. We administered candesartan therapy (12 mg daily) for 6 months and evaluated whether there was improvement in serum inflammatory parameters high molecular weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) in serum and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of lowering of blood pressure and inflammatory factors and the relationship between pulse pressure and inflammatory factors. Finally, we analyzed predictive factors in patients who received the protective benefit of candesartan.. After 6 months of treatment, significant improvements from baseline values were observed in all patients in HMW-ADN and PAI-1 but not in Hs-CRP, VCAM-1 and U-8-OHdG. Multilinear regression analysis was performed to determine which factors could best predict changes in HMW-ADN and PAI-1. Changes in blood pressure were not significant predictors of changes in metabolic factors in all patients. We found that the group with baseline pulse pressure <60 mmHg had improved HMW-ADN and PAI-1 values compared with the group with baseline pulse pressure ≥ 60 mmHg. These results suggest that pulse pressure at baseline could be predictive of changes in HMW-ADN and PAI-1.. Candesartan improved inflammatory parameters (HMW-ADN and PAI-1) in hypertensive patients with type 2 diabetes mellitus of long duration independent of blood pressure changes. Patients with pulse pressure <60 mmHg might receive protective benefits by candesartan.. UMIN000007921.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Biomarkers; Biphenyl Compounds; Blood Pressure; C-Reactive Protein; Deoxyguanosine; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Inflammation; Inflammation Mediators; Japan; Linear Models; Male; Middle Aged; Multivariate Analysis; Plasminogen Activator Inhibitor 1; Prospective Studies; Tetrazoles; Time Factors; Treatment Outcome; Vascular Cell Adhesion Molecule-1

The three types of calcium channel blocker (CCB), L-, T- and N-type, possess heterogeneous actions on endothelial function and renal microvascular function. In the present study, we evaluated the effects of two CCBs, efonidipine and amlodipine, on renal function and arterial stiffness.. Forty type 2 diabetic patients with hypertension and nephropathy receiving angiotensin receptor II blockers were enrolled and randomly divided into two groups: the efonidipine group was administered efonidipine hydrochloride ethanolate 40 mg/day and the amlodipine group was admin-istered amlodipine besilate 5 mg/day for 12 months. Arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI).. Changes in blood pressure during the study were almost the same in the two groups. Sig-nificant increases in serum creatinine and urinary albumin and a significant decrease in the esti-mated glomerular filtration rate were observed in the amlodipine group, but not in the efonidipine group. On the other hand, significant decreases in plasma aldosterone, urinary 8-hydroxy-2'-deoxy-guanosine and CAVI were observed after 12 months in the efonidipine group, but not in the amlo-dipine group.. These results suggest that efonidipine, which is both a T-type and L-type calcium chan-nel blocker, has more favorable effects on renal function, oxidative stress and arterial stiffness than amlodipine, an L-type calcium channel blocker.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldosterone; Amlodipine; Arteries; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dihydropyridines; Female; Glycated Hemoglobin; Humans; Hypertension; Kidney; Lipids; Male; Middle Aged; Nitrophenols; Organophosphorus Compounds

Recently, a novel device for measuring the cardio-ankle vascular index (CAVI) as an arterial stiffness parameter has been developed. In this study, we evaluated the effect of angiotensin II receptor blocker (ARB) and calcium channel (Ca) blocker on CAVI in type 2 diabetic patients with hypertension.. Seventy type 2 diabetes mellitus patients with hypertension were enrolled and randomly divided into two groups. One group was administered olmesartan medoxomil 20 mg/day [DOSAGE ERROR CORRECTED] for 12 months (ARB group), and the other group was administered amlodipine besilate 5 mg/day for 12 months (Ca blocker group).. In the ARB group, a significant decrease in CAVI was observed after 12 months; however, no significant change in CAVI was observed in the Ca blocker group although changes in blood pressure were almost the same. By simple regression analyses, CAVI changes correlated positively with 8-OHdG changes.. Olmesartan, an ARB, improved arterial stiffness more than amlodipine, and this effect might be due to not only the blood pressure-lowering effect but also to reducing the potential of oxidative stress recognized in olmesartan.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Ankle; Antihypertensive Agents; Body Weight; Calcium Channel Blockers; Deoxyguanosine; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypertension; Imidazoles; Lipids; Male; Middle Aged; Tetrazoles

Endothelial function is impaired in hypertensive patients. Decreased nitric oxide production and increased oxidative stress are involved in this abnormality. The aim of the present study was to evaluate whether endothelial function and oxidative stress differ following long-term antihypertensive treatment with an angiotensin type 1 receptor blocker, valsartan, or a calcium channel blocker, amlodipine, in patients with essential hypertension. Hypertensive patients were treated with valsartan (80-160 mg/day) or amlodipine (5-10 mg/day) for one year (n = 9 for each). The baseline blood pressure was similar between groups, and the magnitude of the decreases in blood pressure did not differ during treatment at three months, six months, or one year. Endothelial function and oxidative stress markers were examined before and after treatment. Endothelial function, assessed by flow-mediated vasodilation, was significantly improved in hypertensive patients treated with valsartan (5.8 +/- 1.2 to 10.7 +/- 1.4 %, p < 0.01) but not in those treated with amlodipine. The percent increase in vasodilation induced by sublingual nitroglycerin did not differ between the two groups. As markers of oxidative stress, urinary excretion of 8-isoprostane and 8-hydroxy-2'-deoxyguanosine was significantly reduced in patients treated with valsartan, but not in those treated with amlodipine. These findings suggest that the treatment of hypertensive patients with valsartan for at least one year improves endothelial function in association with reduced oxidative stress. The improved endothelial function and reduced oxidative stress might be involved in the benefits of anti-hypertensive treatment beyond simply lowering blood pressure, although the effects of treatment with valsartan or amlodipine over a much longer period are unknown.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Asian People; Biomarkers; Blood Pressure; Brachial Artery; Calcium Channel Blockers; Deoxyguanosine; Dinoprost; Endothelium, Vascular; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Regional Blood Flow; Tetrazoles; Valine; Valsartan; Vasodilation

Hypoxia plays a significant role in the pathogenesis and progression of chronic renal disease. Urinary liver-type fatty acid binding protein (L-FABP) levels reflect the clinical prognosis of chronic renal disease. The calcium channel blocker azelnidipine has anti-oxidative properties and these may contribute to the beneficial effects of this drug. The aim of the present study was to determine whether azelnidipine and/or amlodipine affected urinary protein excretion or the urinary levels of 8-OHdG and L-FABP in hypertensive patients with mild chronic kidney disease (CKD).. Thirty moderately hypertensive chronic kidney disease patients were randomly assigned to 2 treatment groups: azelnidipine 16 mg once daily or amlodipine 5 mg once daily. Treatment was continued for 6 months. Urinary protein excretion and urinary levels of 8-OHdG and urinary L-FABP were measured before 3 and 6 months after the treatment period.. Both drugs exhibited comparable and significant effects on the systolic and diastolic blood pressure. Azelnidipine decreased heart rate significantly after 3 and 6 months whereas amlodipine increased it significantly after 3 and 6 months. Urinary protein excretion, urinary 8-OHdG and urinary L-FABP levels decreased significantly after 3 months (p < 0.05) and 6 months (p < 0.05) in the azelnidipine group. In contrast, amlodipine showed little effect on urinary protein excretion or the urinary levels of 8-OHdG and L-FABP throughout the experimental period.. Azelnidipine is renoprotective in hypertensive patients with mild CKD and this action is, at least in part, due to the anti-oxidative effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amlodipine; Antioxidants; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Fatty Acid-Binding Proteins; Female; Heart Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria

The purpose of this pilot study was to test whether carvedilol has a protective effect against oxidative deoxyribonucleic acid (DNA) damage in human hypertension in vivo. Carvedilol's antioxidant effect has mostly focused on lipid or amino acid so far. However, there has been no data that carvedilol reduces DNA damage in human hypertension. Never-treated mild to moderate hypertension patients and age- and sex-matched control subjects volunteered for the study. The hypertension subjects were given 12.5 or 25 mg of carvedilol or hydrochlorothiazide orally for 2 months and controls were not given any. Fasting blood samples were collected before and after carvedilol. Plasma highly sensitive 8-hydroxy-2'-deoxyguanosine (hs8-OHdG) and high-sensitivity C-reactive protein (hsCRP) were checked with the samples. There were no statistical differences in clinical characteristics in 3 groups. The hs8-OHdG declined from 9.07+/-4.23 ng/mL to 5.74+/-3.89 ng/mL (P=0.002) after carvedilol. However, it did not show significant reduction after hydrochlorothiazide (9.01+/-3.89 versus 8.23+/-4.12 ng/mL; P=NS). In the control group, the hs8-OHdG concentration was 3.41+/-2.03 ng/mL and 3.01+/-2.65 ng/mL at baseline and 2 months later, respectively (P=NS). The baseline hs8-OHdG levels were higher in hypertension groups compared with control (P=0.000). The hsCRP had no significant difference before and after the tested drugs in 2 hypertension groups (group A: 0.21+/-0.51 versus 0.19+/-0.37 mg/dL; group B: 0.20+/-0.45 versus 0.18+/-0.42 mg/dL). In conclusion, DNA damage caused by reactive oxygen species occurs more in the hypertension patients than normals. Carvedilol significantly reduces DNA damage in the hypertension patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antihypertensive Agents; Antioxidants; C-Reactive Protein; Carbazoles; Carvedilol; Deoxyguanosine; DNA Damage; Double-Blind Method; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Pilot Projects; Propanolamines; Severity of Illness Index

The relationships between stress hormones and oxidative DNA damage have not yet been explored in human hypertension. We investigated the associations of urinary levels of cortisol or catecholamines with those of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage in primary hypertension.. Untreated 156 primary hypertensives without apparent cardiovascular diseases were entered into the study. Following blood sampling after an overnight fast, 24-h blood pressure monitoring and 24-h urinary sampling were performed simultaneously to determine 24-h averaged values for blood pressure and urinary levels of cortisol, catecholamines and 8-hydroxy-2'-deoxyguanosine.. Urinary cortisol significantly correlated positively with urinary 8-hydroxy-2'-deoxyguanosine in all studied participants (r = 0.334, P < 0.001). Contrary, either urinary adrenaline or urinary noradrenaline did not significantly correlate with urinary 8-hydroxy-2'-deoxyguanosine (r = 0.050, P = 0.553 or r = 0.063, P = 0.435). Additionally, the positive association of urinary cortisol with urinary 8-hydroxy-2'-deoxyguanosine remained highly significant after the adjustments for multiple confounders of oxidative stress such as age, gender, body mass index, smoking status, 24-h blood pressure, C-reactive protein and estimated glomerular filtration rate (partial r = 0.323, P < 0.001), although only approximately 10% of the variance in urinary cortisol was attributable to differences in urinary 8-OHdG (partial r2 = 0.104). Thus, our data indicate that cortisol but not catecholamines could at least partially contribute to the occurrence of oxidative DNA damage in primary hypertensives.. The present study suggested the possibility that the overactivation of hypothalamic-pituitary-adrenal axis rather than sympathoadrenal system could enhance oxidative stress and attendant DNA oxidation in uncomplicated primary hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Catecholamines; Essential Hypertension; Humans; Hydrocortisone; Hypertension; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System

Oxidative stress plays a pivotal role in the pathogenesis of pulmonary arterial hypertension. 8-Hydroxy-2'-deoxyguanosine is a sensitive biomarker that reflects the degree of oxidative damage to DNA. We investigated whether serum 8-Hydroxy-2'-deoxyguanosine is a clinically useful biomarker for the severity of pulmonary arterial hypertension.. We measured serum 8-Hydroxy-2'-deoxyguanosine levels in 25 patients (age 37±13 years, 68% women) diagnosed with idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease. The severity of pulmonary arterial hypertension was evaluated by six-min walking distance, World Health Organization functional class, and serum brain natriuretic peptide levels. Age and gender-matched 22 healthy subjects served as the control group.. The comparison of 8-Hydroxy-2'-deoxyguanosine levels between patients and controls was not statistically different [(19.86±9.79) versus (18.80±3.94) ng/mL, p=0.622)]. However, there was a significant negative correlation between 8-Hydroxy-2'-deoxyguanosine levels and six-min walking distance (r= -0.614, p=0.001). Additionally, serum 8-Hydroxy-2'-deoxyguanosine levels in patients with functional class III-IV were significantly higher than those with functional class I-II (functional class III-IV 32.31±10.63 ng/mL versus functional class I-II 16.74±6.81 ng/mL, respectively, p=0.003).. The 8-Hydroxy-2'-deoxyguanosine levels were significantly correlated with exercise capacity (six-min walking distance) and symptomatic status (functional class), both of which show the severity of pulmonary arterial hypertension in patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Pulmonary Arterial Hypertension; Young Adult

The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice.. Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice.. No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress.. We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Animals, Newborn; Aorta; Blood Pressure; Caffeine; Corticosterone; Feces; Female; Hypertension; Male; Mice; Norepinephrine; Risk Factors; Sex Factors; Stress, Physiological; Vasoconstriction

Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Carcinoma, Renal Cell; Case-Control Studies; Deoxyguanosine; Female; Genetic Predisposition to Disease; Glutathione Transferase; Haplotypes; Humans; Hypertension; Kidney Neoplasms; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Risk Factors

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensins; Animals; Arginine; Cardiovascular Diseases; Deoxyguanosine; Disease Models, Animal; Humans; Hypertension; Hypoxia; Kidney; Male; Mice; Mice, Inbred C57BL; Norepinephrine; Oxidative Stress; Sympathectomy; Sympathetic Nervous System

Studies have suggested that the consumption of green tea reduces the risk of cardiovascular diseases. Although epigallocatechin gallate (EGCG) is the best studied active substance characteristic of green tea, previous results on EGCG do not appear sufficient to explain completely the mechanism of cardiovascular protection by green tea. Therefore, we investigated the effect of three different tea cultivars, "Yabukita," "Sofu," and "Sunrouge," which have characteristic flavonoid compositions, on the nitric oxide (NO) production and the related protein expression in the aorta of spontaneously hypertensive rats (SHRs) fed a high-salt diet. As a result, the reduction of urinary NO metabolite (NOx) levels, which reflect whole-body NO production, caused by the high-salt diet were significantly prevented by all three tea infusions. The improvement of NOx reduction in the tea-intake groups was unlikely to be caused by the changes in oxidative damage. On the other hand, as a partial effect, only "Yabukita" or "Sofu" increased the expression of the soluble guanylate cyclase, a receptor for NO, in the thoracic aorta. In the present study, the differences in the composition of these three cultivars led to partially different effects on NO signaling in SHRs, suggesting the physiological significance of subdominant ingredients besides EGCG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Aorta, Thoracic; Biomarkers; Camellia sinensis; Deoxyguanosine; Endothelium, Vascular; Food Handling; Functional Food; Hypertension; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidation-Reduction; Plant Leaves; Rats, Inbred SHR; Reproducibility of Results; Sodium Chloride, Dietary; Soluble Guanylyl Cyclase; Species Specificity; Tea

This study aimed to evaluate the role of protein oxidation and DNA damage in the elderly hypertensive (HT) patients.. This study consisted of four groups: two elderly groups with 30 HT patients and 30 normotensive healthy volunteers, and two young groups with 30 HT patients and 30 normotensive healthy volunteers. Plasma total thiol (T-SH), advanced oxidation protein products (AOPPs), protein carbonyl (PCO), ischemia modified albumin (IMA), urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), and prooxidant-antioxidant balance (PAB) levels were measured.. In the elderly HT group AOPPs, PCO, 8-OHdG, and PAB were significantly higher than the elderly control group. In the young HT group T-SH levels were significantly lower and the other oxidative stress parameters were significantly higher than the young control group. In the elderly control group AOPPs, PCO, IMA, 8-OHdG and PAB were significantly higher than the young control group. T-SH was significantly lower in the elderly control than the young control group. In the elderly HT group, T-SH levels were significantly lower and AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher than the young HT group.. Protein and DNA cell damage occurs by oxidation of free radicals throughout life. Our study supports the view that these radicals may be responsible for the development of hypertension with aging process. Urine 8-OHdG levels can be used as a marker for oxidative DNA damage in the elderly hypertensive patients. Finally, our results suggest that oxidative stress may influence both the development and progression of hypertension and aging.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Aging; Antioxidants; Biomarkers; Deoxyguanosine; DNA Damage; Female; Free Radicals; Humans; Hypertension; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Serum Albumin; Serum Albumin, Human; Sulfhydryl Compounds

Chronic kidney disease (CKD) is associated with an inflammation-mediated process, and the vitamin D (3) catabolizing enzyme, CYP24, is frequently overexpressed in CKD, where it may play a crucial role in kidney disease.. Herein, in this study, we investigated CYP24, reactive oxygen species (ROS), and inflammatory responses in an indoxyl sulfate (IS)-induced CKD model to elucidate the role of CYP24 in CKD.. Our results showed that IS upregulates proinflammatory cytokine, CYP24 and nuclear factor-κB (NF-κB) expression in human renal proximal tubule epithelial cells. In addition, IS treatment increased ROS production and simultaneously upregulated CYP24 expression and NF-κB translocation. Moreover, the IS-induced upregulation of CYP24 expression was alleviated by an inhibitor of NF-κB, as well as a siRNA specific to NF-κB p65. Furthermore, the renal cortex of DN (Dahl salt-resistant normotensive) + IS, DH (Dahl salt-sensitive hypertensive), and DH + IS rats showed increased expression of NF-κB p65, CYP24, 8-hydroxydeoxyguanosine (8-OHdG), a marker of ROS and macrophage infiltration compared with DN rats.. These results provide evidence that administration of IS in human renal tubular epithelial cells upregulates NF-κB, which leads to increase CYP24 expression and ROS production. They also suggest that suppressing NF-κB signalling is promising for the development into a strategy for CKD treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Line, Tumor; Cytochrome P450 Family 24; Cytokines; Deoxyguanosine; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypertension; Indican; Inflammation Mediators; Kidney; Oxidative Stress; Rats, Inbred Dahl; Reactive Oxygen Species; Renal Insufficiency, Chronic; RNA Interference; Transcription Factor RelA; Transfection; Up-Regulation

Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two-kidney, one-clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α-lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed. In addition, insulin secretion from islet cells was measured. OGTT yielded abnormal results, and the number of islet cells and the size of pancreatic β/α cells were decreased in 2K1C rats. Basal insulin levels were also reduced in the plasma. Insulin secretion from pancreatic islet cells in response to high glucose was also attenuated in 2K1C rats compared with sham rats. The levels of oxidative stress markers, including 8-hydroxydeoxyguanosine and NADPH oxidase-4, were increased in pancreatic tissue and pancreatic islets in 2K1C rats. The abnormalities observed in 2K1C rats were improved by captopril or α-lipoic acid treatment. These findings indicate that sustained renal hypertension may lead to pancreatic dysfunction, increasing oxidative stress in pancreatic islets.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Captopril; Deoxyguanosine; Diabetes Mellitus; Hypertension; Insulin; Insulin Secretion; Insulin-Secreting Cells; Kidney; Male; Models, Animal; NADPH Oxidase 4; NADPH Oxidases; Oxidative Stress; Pancreas; Rats; Rats, Sprague-Dawley; Thioctic Acid

Nitric oxide (NO) deficiency occurs in humans and animals with hypertension and chronic kidney disease (CKD). An inhibitor of NO synthase, N(G)-nitro-l-arginine methyl ester (L-NAME) exacerbates kidney damage in the adult spontaneously hypertensive rat (SHR). We examined whether L-NAME exacerbated hypertensive nephrosclerosis in young SHRs and whether melatonin protects SHRs against kidney damage by restoration of the asymmetric dimethylarginine (ADMA)-NO pathway.. Rats aged 4 weeks were randomly assigned into three groups (n = 10 for each group): Group 1 (control), SHRs without treatment; Group 2 (L-NAME), SHRs received L-NAME (80 mg/L) in drinking water; and Group 3 (L-NAME + melatonin), SHRs received L-NAME (80 mg/L) and 0.01% melatonin in drinking water. All rats were sacrificed at 10 weeks of age.. L-NAME exacerbates the elevation of blood pressure, renal dysfunction, and glomerular sclerosis in young SHRs. L-NAME induced an increase of ADMA and a decrease of arginine-to-ADMA ratio in the SHR kidney. Melatonin therapy prevented L-NAME-exacerbated hypertension and nephrosclerosis in young SHRs. In addition, melatonin restored L-NAME-induced reduction of dimethylarginine dimethylaminohydrolase (DDAH; ADMA-metabolizing enzymes) activity in the SHR kidney. Next, melatonin decreased renal ADMA concentrations, increased renal arginine-to-ADMA ratio, and restored NO production in L-NAME-treated young SHRs. Moreover, melatonin reduced the degree of oxidative damaged DNA product, 8-hydroxydeoxyguanosine immunostaining in L-NAME-treated SHR kidney.. Our results indicated that L-NAME/SHR is a useful model for hypertensive nephrosclerosis in young rats. The blood pressure-lowering and renoprotective effects of melatonin is due to increases of DDAH activity, decreases of ADMA, and reduction of oxidative stress in L-NAME-treated SHR kidney. Specific therapy targeting the DDAH-ADMA pathway may be a promising approach to slowing chronic kidney disease progression in children.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amidohydrolases; Animals; Antioxidants; Arginine; Blood Pressure; Deoxyguanosine; Humans; Hypertension; Hypertension, Renal; Kidney; Male; Melatonin; Nephritis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Inbred SHR

Oxidative stress, assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state.. Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT.. There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β= 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT.. In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Ankle Brachial Index; Cohort Studies; Deoxyguanosine; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Pulse Wave Analysis; Vascular Stiffness

Experiments determined whether the combination of endothelin A (ETA) receptor antagonist [ABT-627, atrasentan; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid] and a thiazide diuretic (chlorthalidone) would be more effective at lowering blood pressure and reducing renal injury in a rodent model of metabolic syndrome compared with either treatment alone. Male Dahl salt-sensitive rats were fed a high-fat (36% fat), high-salt (4% NaCl) diet for 4 weeks. Separate groups of rats were then treated with vehicle (control), ABT-627 (ABT; 5 mg/kg per day, in drinking water), chlorthalidone (CLTD; 5 mg/kg per day, in drinking water), or both ABT plus CLTD. Mean arterial pressure (MAP) was recorded continuously by telemetry. After 4 weeks, both ABT and CLTD severely attenuated the development of hypertension, whereas the combination further reduced MAP compared with ABT alone. All treatments prevented proteinuria. CLTD and ABT plus CLTD significantly reduced nephrin (a podocyte injury marker) and kidney injury molecule-1 (a tubulointerstitial injury marker) excretion. ABT, with or without CLTD, significantly reduced plasma 8-oxo-2'-deoxyguanosine, a measure of DNA oxidation, whereas CLTD alone had no effect. All treatments suppressed the number of ED1(+) cells (macrophages) in the kidney. Plasma tumor necrosis factor receptors 1 and 2 were reduced only in the combined ABT and CLTD group. These results suggest that ABT and CLTD have antihypertensive and renal-protective effects in a model of metabolic syndrome that are maximally effective when both drugs are administered together. The findings support the hypothesis that combined ETA antagonist and diuretic treatment may provide therapeutic benefit for individuals with metabolic syndrome consuming a Western diet.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Arterial Pressure; Atrasentan; Cell Adhesion Molecules; Chlorthalidone; Deoxyguanosine; Disease Models, Animal; Diuretics; Drug Combinations; Endothelin A Receptor Antagonists; Endothelins; Hypertension; Inflammation; Kidney Diseases; Male; Membrane Proteins; Metabolic Syndrome; Oxidative Stress; Proteinuria; Pyrrolidines; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Receptor, Endothelin A; Sodium Chloride, Dietary

Recently, we could show that angiotensin II, the reactive peptide of the blood pressure-regulating renin-angiotensin-aldosterone-system, causes the formation of reactive oxygen species and DNA damage in kidneys and hearts of hypertensive mice. To further investigate on the one hand the mechanism of DNA damage caused by angiotensin II, and on the other hand possible intervention strategies against end-organ damage, the effects of substances interfering with the renin-angiotensin-aldosterone-system on angiotensin II-induced genomic damage were studied.. In C57BL/6-mice, hypertension was induced by infusion of 600 ng/kg • min angiotensin II. The animals were additionally treated with the angiotensin II type 1 receptor blocker candesartan, the mineralocorticoid receptor blocker eplerenone and the antioxidant tempol. DNA damage and the activation of transcription factors were studied by immunohistochemistry and protein expression analysis.. Administration of angiotensin II led to a significant increase of blood pressure, decreased only by candesartan. In kidneys and hearts of angiotensin II-treated animals, significant oxidative stress could be detected (1.5-fold over control). The redox-sensitive transcription factors Nrf2 and NF-κB were activated in the kidney by angiotensin II-treatment (4- and 3-fold over control, respectively) and reduced by all interventions. In kidneys and hearts an increase of DNA damage (3- and 2-fold over control, respectively) and of DNA repair (3-fold over control) was found. These effects were ameliorated by all interventions in both organs. Consistently, candesartan and tempol were more effective than eplerenone.. Angiotensin II-induced DNA damage is caused by angiotensin II type 1 receptor-mediated formation of oxidative stress in vivo. The angiotensin II-mediated physiological increase of aldosterone adds to the DNA-damaging effects. Blocking angiotensin II and mineralocorticoid receptors therefore has beneficial effects on end-organ damage independent of blood pressure normalization.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Antioxidants; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Cyclic N-Oxides; Deoxyguanosine; DNA Damage; DNA Repair; Enzyme Activation; Eplerenone; Guanosine; Heart; Hypertension; Kidney; Male; Mice; Mice, Inbred C57BL; Mineralocorticoid Receptor Antagonists; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Renin-Angiotensin System; Spin Labels; Spironolactone; Tetrazoles

Aging-associated declines in cognitive, emotional, and cardiovascular function are well known. Environmental stress triggers critical changes in the brain, further compromising cardiovascular and behavioral health during aging. Excessive dietary salt intake is one such stressor. Here, we tested the effect of high salt (HS) on anxiety, learning-memory function, and blood pressure (BP) in male Fischer brown Norway (FBN) rats. Adult (A; 2 mo) and old (O; 20 mo) male rats were fed normal-salt (NS; 0.4% NaCl) or HS (8% NaCl) diets for 4 wk after being implanted with telemeter probes for conscious BP measurement. Thereafter, tests to assess anxiety-like behavior and learning-memory were conducted. The rats were then killed, and samples of plasma, urine, and brain tissue were collected. We found that systolic BP was higher in O-NS (117 ± 1.2 mm Hg) than in A-NS (105 ± 0.8 mm Hg) rats (P < 0.05). Furthermore, BP was higher in O-HS (124 ± 1.4 mm Hg) than in O-NS (117 ± 1.2 mm Hg) rats (P < 0.05). Moreover, anxiety-like behavior (light-dark and open-field tests) was not different between A-NS and O-NS rats but was greater in O-HS rats than in A-NS, O-NS, or A-HS rats (P < 0.05). Short-term memory (radial arm water maze test) was similar in A-NS and O-NS rats but was significantly impaired in O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05). Furthermore, oxidative stress variables (in plasma, urine, and brain) as well as corticosterone (plasma) were greater in O-HS rats when compared with A-NS, O-NS, or A-HS rats (P < 0.05). The antioxidant enzyme glyoxalase-1 expression was selectively reduced in the hippocampus and amygdala of O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05), whereas other antioxidant enzymes, glutathione reductase 1, manganese superoxide dismutase (SOD), and Cu/Zn SOD remained unchanged. We suggest that salt-sensitive hypertension and behavioral derangement are associated with a redox imbalance in the brain of aged FBN rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Anxiety; Blood Pressure; Corticosterone; Deoxyguanosine; Diet; Dinoprost; Disease Models, Animal; Gene Expression Regulation; Glutathione Reductase; Hypertension; Lactoylglutathione Lyase; Learning; Male; Memory, Short-Term; Oxidative Stress; Rats; Sodium Chloride, Dietary; Superoxide Dismutase

To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier (BBB) dysfunction, we compared the chronological changes of oxidative stress in blood and cerebral tissue between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age, but not in WKY. There were no significant differences in 8-OHdG or lipid peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by the biological antioxidant potential test, was similar between SHRSP and WKY at all ages examined. The changes in plasma and tissue d-ROM levels coincided with changes in glucose transporter-1 and aquaporin-4 expression, as functional constituents of the BBB. These results indicate that plasma oxidative stress increases before the onset of tissue damage, and plays an important role in BBB dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test appears to be useful for predicting vasogenic cerebral edema in severe hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Aquaporin 4; Biomarkers; Blood Pressure; Blood-Brain Barrier; Body Weight; Brain Edema; Capillary Permeability; Deoxyguanosine; Disease Models, Animal; Glucose Transporter Type 1; Hypertension; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Time Factors

In this work, a new, fast and reliable methodology using a digitally controlled microextraction by packed sorbent (eVol(®)-MEPS) followed by ultra-high pressure liquid chromatography (UHPLC) analysis with photodiodes (PDA) detection, was developed to establish the urinary profile levels of four putative oxidative stress biomarkers (OSBs) in healthy subjects and patients evidencing cardiovascular diseases (CVDs). This data was used to verify the suitability of the selected OSBs (uric acid-UAc, malondialdehyde-MDA, 5-(hydroxymethyl)uracil-5-HMUra and 8-hydroxy-2'-deoxyguanosine-8-oxodG) as potential biomarkers of CVDs progression. Important parameters affecting the efficiency of the extraction process were optimized, particularly stationary phase selection, pH influence, sample volume, number of extraction cycles and washing and elution volumes. The experimental conditions that allowed the best extraction efficiency, expressed in terms of total area of the target analytes and data reproducibility, includes a 10 times dilution and pH adjustment of the urine samples to 6.0, followed by a gradient elution through the C8 adsorbent with 5 times 50 µL of 0.01% formic acid and 3×50 µL of 20% methanol in 0.01% formic acid. The chromatographic separation of the target analytes was performed with a HSS T3 column (100 mm × 2.1 mm, 1.7 µm in particle size) using 0.01% formic acid 20% methanol at 250 µL min(-1). The methodology was validated in terms of selectivity, linearity, instrumental limit of detection (LOD), method limit of quantification (LOQ), matrix effect, accuracy and precision (intra-and inter-day). Good results were obtained in terms of selectivity and linearity (r(2)>0.9906), as well as the LOD and LOQ, whose values were low, ranging from 0.00005 to 0.72 µg mL(-1) and 0.00023 to 2.31 µg mL(-1), respectively. The recovery results (91.1-123.0%), intra-day (1.0-8.3%), inter-day precision (4.6-6.3%) and the matrix effect (60.1-110.3%) of eVol(®)-MEPS/UHPLC-PDA method were also very satisfactory. Finally, the application of the methodology to the determination of target biomarkers in normal subjects and CVDs patients' revealed that the DNA adducts 5-HMUra and 8-oxodG levels are much more abundant in CVDs patients while no statistic differences were obtain for MDA and UAc. This result points to the importance of 5-HMUra and 8-oxodG as biomarkers of CVDs risk progression and further epidemiological studies are needed to explore the importance of this correlation

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Calibration; Case-Control Studies; Chromatography, High Pressure Liquid; Deoxyguanosine; Disease Progression; Female; Humans; Hydrogen-Ion Concentration; Hypercholesterolemia; Hypertension; Limit of Detection; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Pentoxyl; Reproducibility of Results; Risk Factors; Solid Phase Microextraction; Uric Acid

This study investigated whether the angiotensin II type-1 receptor blocker (ARB) candesartan affects markers of oxidative stress in type 2 diabetes mellitus (DM) patients with essential hypertension (EH).. Urinary excretion of pyrraline (PR), pentosidine (PT), acrolein (AC), and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and microalbuminuria were assessed in patients with DM complicated by EH who were treated with candesartan 4 mg/day for 3 months.. In a total of 25 patients urinary excretion of PR (nmol/g · cr), PT (pmol/g · cr), and 8-OH-dG (ng/mg · cr) was significantly (all P < 0.05) decreased from (mean ± SEM) 11.9 ± 1.9, 30.6 ± 2.4, and 7.9 ± 0.6, respectively, at baseline to 8.4 ± 1.4, 27.1 ± 2.0, and 6.9 ± 0.6, respectively, at 3 months. Meanwhile, excretion of AC was unaltered from 209.6 ± 40.0 to 189 ± 24.8 nmol/mgcr (P = NS). Urinary albumin excretion was significantly (P < 0.05) reduced from 27.7 ± 4.6 to 14.1 ± 1.1 mg/g · cr. There were weak but statistically significant positive correlations between the change of urinary 8-OH-dG excretion and that of albumin (r = 0.414; P < 0.05) and change of hemoglobin (Hb) A1c (r = 0.45; P < 0.05).. Candesartan exerts protective effect(s) on the cardiovascular system by suppression of oxidative stress--mainly through inhibiting production of advanced glycation end products (AGEs) rather than of advanced lipoxidation end products (ALEs)--in type 2 DM patients with EH.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Deoxyguanosine; Diabetes Mellitus, Type 2; Essential Hypertension; Female; Glycation End Products, Advanced; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Tetrazoles

This study examined the effects of continual Gram-negative bacterial challenge on stroke onset. Stroke onset occurred significantly earlier in stroke-prone spontaneously hypertensive rats (SHRSP) injected with a bacterial cell suspension of Gram-negative rods or lipopolysaccharides (LPSs) than in uninjected controls. Paralysis of the hindlimb, piloerection, hypokinesis, and hyperkinesis were observed in LPS-injected SHRSP but not in uninjected controls during stroke onset. The serum levels of NOx, thiobarbituric acid reactive substance, and 8-hydroxydeoxyguanosine increased in LPS-injected SHRSP. These results suggest that continual Gram-negative bacterial challenge induces accelerated stroke onset in SHRSP, probably caused by oxidative stress responses derived from LPSs.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Animals; Biomarkers; Blood Pressure; Brain; Deoxyguanosine; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hypertension; Lipopolysaccharides; Nitrogen Oxides; Rats; Rats, Inbred SHR; Stroke; Thiobarbituric Acid Reactive Substances

Although increased oxidative stress is known to be associated with worsened cardiac function in chronic heart failure, consensus is still lacking regarding the association between oxidative stress and cardiac function in hypertensive patients without overt heart disease. This study aimed to evaluate the association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine (8-OHdG) and cardiac function in hypertensive patients without overt heart disease. We enrolled a total of 80 hypertensive patients (70 ± 11 y) who had been taking antihypertensive medications for at least 1 year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001, Selista Inc., Tokyo, Japan). Echocardiography was performed to assess the left ventricular (LV) diastolic function by measuring early diastolic mitral annular velocity (e') and the ratio of early transmitral flow velocity (E) to e' (E/e'). Urinary 8-OHdG was correlated with E/e' (r = 0.346, P = .002), e' (r = -0.310, P = .005), and HbA1c (r = 0.276, P = .013). Multiple linear regression analysis revealed that only e' (β = -0.343, P = .004) was an independent determinant of urinary 8-OHdG. In conclusion, decreased e' is independently associated with elevated urinary 8-OHdG, a marker of oxidative stress, in hypertensive patients. Therefore, an elevated urinary 8-OHdG level may be useful in detecting subclinical LV diastolic dysfunction in hypertensive patients without overt heart disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Cross-Sectional Studies; Deoxyguanosine; Echocardiography; Female; Heart; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Ventricular Function, Left

The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT.. We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined.. 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine.. Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Deoxyguanosine; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Interleukin-6; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Risk Factors; Tumor Necrosis Factor-alpha

The effects of hesperidin, glucosyl hesperidin (G-hesperidin), a water-soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke-prone spontaneously hypertensive rats (SHRSP). Hesperidin, G-hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure. Thrombotic tendency, as assessed using a He-Ne laser technique in the cerebral blood vessels, was significantly decreased in the treated animals compared with the control animals. Measurements of 8-hydroxy-2'-deoxyguanosine (8-OHdG) demonstrated that the supplements had strong antioxidant activity. Furthermore, these supplements significantly increased the production of nitric oxide (NO) metabolites in urine measured with Griess reagent. Vasodilation induced by acetylcholine-mediated NO production in the endothelium was assessed using thoracic aortic ring preparations and indicated that endothelial function was significantly improved by the administration of these supplements. These findings suggest that the strong antioxidant properties of hesperidin, G-hesperidin and naringin could modulate the inactivation of NO and protect endothelial function from reactive oxygen species (ROS). In this manner, the flavonoids could contribute beneficial effects on the mechanisms of hypertension and thrombosis by increasing the bioavailability of NO.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Body Weight; Deoxyguanosine; Flavanones; Glucosides; Hesperidin; Hypertension; Intracranial Thrombosis; Male; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred SHR; Vasodilation

Oxidative stress has been recently postulated to be an important factor in the pathogenesis and development of arteriosclerosis. Although urinary 8-hydroxydeoxyguanosine (8-OHdG) is clinically used as a marker of oxidative stress, its usefulness in diagnosing arteriosclerosis has not been fully examined. This study aimed to evaluate the association between urinary 8-OHdG and the cardioankle vascular index (CAVI) as a marker of arterial stiffness in hypertensive patients.. We enrolled 100 hypertensive patients (70 ± 10 years) who had been taking antihypertensive medications for at least one year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001; Selista Inc., Tokyo, Japan). CAVIs were measured at the same visit.. Urinary 8-OHdG was correlated with smoking habits (r=0.382, p<0.001) and CAVIs (r= 0.223, p= 0.026). Multiple linear regression analysis revealed two independent determinants of urinary 8-OHdG: smoking habits (β=0.501, p<0.001) and CAVI (β=0.325, p=0.001). In addition, CAVIs were correlated with age (r= 0.600, p<0.001), BMI (r=-0.348, p<0.001), systolic blood pressure (r= 0.343, p<0.001), pulse pressure (r= 0.358, p<0.001), serum creatinine level (r=0.408, p<0.001), urinary 8-OHdG level (r= 0.223, p= 0.026), and diabetes (r= 0.210, p=0.036). Multiple linear regression analysis revealed two independent determinants of CAVI: age (β= 0.568, p<0.001) and 8-OHdG (β=0.357, p<0.001).. Elevated CAVI is independently associated with an elevated urinary 8-OHdG level in hypertensive patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Ankle Brachial Index; Ankle Joint; Biomarkers; Cross-Sectional Studies; Deoxyguanosine; Female; Humans; Hypertension; Japan; Male; Middle Aged; Oxidative Stress; Prognosis; Vascular Stiffness

To assess the association of single-nucleotide polymorphisms (SNPs) in genes codifying for antioxidant enzymes to blood pressure (BP) values and risk of hypertension.. Population-based study including 1388 participants (704 women) older than 18 years in which 300 were untreated hypertensive patients. In 335 untreated hypertensive patients referred to one hypertension clinic, the study was replicated. Thirty-five SNP throughout 13 genes were analyzed using SNPlex. In a subgroup of hypertensive patients, the amount of 8-oxo-deoxyguanosine and GPX activity levels was measured in mononuclear cells.. In the general population, genotypes with the G allele of the c.172G>A polymorphism in the SOD3 gene and those with the T allele of the c.-20C>T polymorphism in the CAT gene were associated with significant lower values of BP. Likewise, these genotypes were associated with less risk for hypertension after adjusting for confounder variables. Haplotypes in both genes increased the strength of associations. In the hypertensive patients, the same alleles of the two polymorphisms were associated with lower BP values too. In addition, two others, the CT-TT genotypes of the c.891C>T polymorphism in the GPX1 gene and the CT-CC genotypes of the c.-793T>C polymorphism of the TXN gene were also significantly associated to lower BP values. Furthermore, the CC genotype of the c.891C>T polymorphism in the GPX1 gene was associated with higher values of 8-oxo-dG and GPX activity levels as compared to those for the CT-TT genotype.. The results of the present study support the influence of antioxidant enzyme genes in BP values and hypertension risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Blood Pressure; Catalase; Deoxyguanosine; Female; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Haplotypes; Humans; Hypertension; Male; Middle Aged; Oxidative Stress; Polymorphism, Single Nucleotide; Risk; Superoxide Dismutase

The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiovascular Diseases; Catalase; Deoxyguanosine; Female; Gene Expression Profiling; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Synthase; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Hypertension; Male; Malondialdehyde; Middle Aged; NADPH Oxidases; Oxidative Stress; Phosphoproteins; Risk Factors; Superoxide Dismutase

It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group. The treated animals were given either astaxanthin or vitamin E for 3 weeks. Body weights in each group were not significantly different from control group during the treatment period, but the usual increase in systolic blood pressure in SHRSP observed with age was significantly suppressed by treatment. Thrombogenesis, assessed using a helium-neon (He-Ne) laser technique in pial blood vessels, together with antioxidant activity, assessed by measuring urinary 8-OHdG levels, were significantly moderated. Urinary nitric oxide (NO) metabolites were increased after treatment. These results supported our hypothesis and strongly suggested that the antithrombotic and antihypertensive effects of astaxanthin or vitamin E may be related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Cardiovascular Diseases; Deoxyguanosine; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Rats; Rats, Inbred SHR; Risk Factors; Specific Pathogen-Free Organisms; Stroke; Xanthophylls

We have demonstrated previously that both acute and chronic oral administration of adenosine have novel functions such as anti-hypertensive effects and improved hyperlipidaemia in stroke-prone spontaneously hypertensive rats (SHRSP) fed a normal diet. The purpose of the present study was to investigate the effect of adenosine administration on metabolic syndrome-related parameters in SHRSP fed a high-fat diet. Six-week-old rats were divided into three groups, and were administered either water (control) or adenosine (10 or 100 mg/l) for 8 weeks. During this period, the rats had free access to a high-fat diet based on AIN-93M. The results showed that hypertension, plasma lipid, NO, insulin, glucose and urinary 8-hydroxy-2'-deoxyguanosine levels improved significantly in both adenosine groups. The mRNA expression levels of genes involved in anti-oxidative activity and adenosine receptors were also altered in the adenosine groups. Administration of adenosine also increased plasma adiponectin levels, accompanied by upregulation of mRNA expression level of adiponectin and adiponectin receptor 1 in perirenal fat and adiponectin receptor 2 in the liver. In conclusion, oral administration of adenosine is effective for improving metabolic syndrome-related parameters in SHRSP, and accordingly it may prevent the progression of the metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenosine; Adiponectin; Adipose Tissue; Animals; Antioxidants; Blood Glucose; Cardiovascular Agents; Deoxyguanosine; Dietary Fats; Enzymes; Gene Expression; Gene Expression Regulation; Hypertension; Insulin; Kidney; Lipids; Liver; Male; Metabolic Syndrome; Nitric Oxide; Rats; Rats, Inbred SHR; Receptors, Adiponectin; RNA, Messenger; Stroke

Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Azetidinecarboxylic Acid; Biomarkers; C-Reactive Protein; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Female; Humans; Hypertension; In Vitro Techniques; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress

Excessive prepubertal salt intake permanently increases blood pressure (BP). We examined the role that the mineralocorticoid receptor (MR) plays in the salt-induced hypertension and renal damage of prepubertal Dahl salt-sensitive (SS) rats.. Prepubertal (6 weeks old) and adult (10 weeks old) Dahl SS rats fed a high (8.0%) salt (HS) diet for 10 weeks were compared in terms of BP and renal function. The effect of treatment between the ages of 4 and 10 weeks with the MR antagonist eplerenone (0.125% in chow), the vasodilator hydralazine (50 mg/kg/day in drinking water) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (tempol) (0.6 mmol/kg/day in drinking water) on the BP and renal function of prepubertal rats fed a HS diet for 10 weeks was also examined.. Excessive salt intake starting in prepuberty was associated with a higher BP increase and greater proteinuria than if it started in adulthood. Eplerenone moderately reduced BP and markedly improved renal injury during its administration in prepubertal rats. These effects continued after drug discontinuation. Hydralazine greatly decreased BP and reduced proteinuria, but these effects were completely lost after drug discontinuation. Excessive salt increased urinary 8-hydroxy-2'-deoxyguanosine levels, intrarenal macrophage infiltration and renal plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA expression. Eplerenone, but not hydralazine, attenuated these salt-induced inflammatory reactions. Tempol improved salt-induced hypertension and renal injury, even after its discontinuation.. Dahl SS rats exposed to excessive salt in prepubescence show a permanent increase in susceptibility to salt-induced hypertension and proteinuria. MR activation may promote these effects at least in part by inducing oxidation and inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Cyclic N-Oxides; Deoxyguanosine; Eplerenone; Hydralazine; Hypertension; Kidney; Male; Mineralocorticoid Receptor Antagonists; Rats; Rats, Inbred Dahl; Receptors, Mineralocorticoid; Renal Insufficiency; Sodium Chloride, Dietary; Spin Labels; Spironolactone

To investigate the association between particulate matter (PM2.5) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals.. Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM2.5 was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG.. Exposure to PM2.5 was associated with a decrease in 8-OHdG in hypertensives compared with an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day.. The results suggest modification of the association between PM2.5 exposure and urinary 8-OHdG by hypertension status. Antioxidant activity present in antihypertensive medications may play a role or PM2.5 exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Air Pollutants; Case-Control Studies; Deoxyguanosine; DNA Damage; Female; Humans; Hypertension; Male; Middle Aged; Oxidation-Reduction; Particulate Matter; Young Adult

The aim of this study was to evaluate the oxidative DNA damage, antioxidant activity, and effects of antihypertensive drugs on oxidative stress in hypertensive patients with different stages of chronic kidney disease (CKD). Fifty-three non-dialyzed hypertensive CKD patients were included by the study. Serum and urinary 8-hydroxydeoxy guanosine (8-OHdG) levels (as a marker of oxidative DNA damage), serum superoxide dismutase (SOD), and glutathione peroxidase (G-Px) activities (as antioxidant enzymes) were measured. SOD activity was higher and G-Px activity was lower in the patient group as compared to control group. Serum and urinary 8-OHdG levels were found to be higher in the patients with proteinuria greater than 3 g/day than those in the patients with proteinuria less than 3 g/day. It has been determined that G-Px activity and urinary 8-OHdG level were lower in the patients treated with angiotensin-converting enzyme (ACE) inhibitor compared to patients treated with calcium channel blocker. The present data show oxidative DNA damage at a higher level in the patients with proteinuria greater than 3 g/day. In comparison to a calcium channel blocker, an ACE inhibitor seems much more protective against oxidative DNA damage in hypertensive patients with different stages of CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Deoxyguanosine; DNA Damage; Female; Glutathione Peroxidase; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Superoxide Dismutase; Young Adult

Glucosyl hesperidin (G-hesperidin), a water-soluble hesperidin derivative, has antihypertensive effects. A detailed understanding of the mechanism of the blood pressure-lowering effect, however, remains obscure. The aim of this work was to investigate the underlying mechanisms involved in the hypotensive effect of G-hesperidin in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs).. Fourteen-week-old SHRs and WKYs were fed a control or G-hesperidin (50 mg/kg) diet for 8 wk. Blood pressure was recorded weekly. After 8 wk, the vasodilatory responses of isolated aortas to acetylcholine and sodium nitroprusside were assessed. Expression of mRNAs related to regulation of blood pressure and vascular tone in the aorta also was investigated. Urinary 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker, was measured. Cardiac and vascular hypertrophies were observed.. In SHRs, the ingestion of G-hesperidin inhibited the development of hypertension. G-hesperidin enhanced endothelium-dependent vasodilation in response to acetylcholine, but had no effect on endothelium-independent vasodilation in response to sodium nitroprusside. G-hesperidin decreased mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase subunits in aorta, which are the main source of superoxide anion in the vasculature; endothelial nitric oxide synthase expression was unchanged. Urinary 8-hydroxy-2'-deoxyguanosine was reduced significantly by G-hesperidin treatment. G-hesperidin suppressed cardiac and vascular hypertrophies. In contrast, G-hesperidin had no effects in WKYs.. Continuous ingestion of G-hesperidin reduces oxidative stress by inhibiting nicotinamide adenine dinucleotide phosphate oxidase expression in the vasculature, thereby ameliorating endothelial dysfunction and hypertension in SHRs.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Aorta; Blood Pressure; Deoxyguanosine; Endothelium, Vascular; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Glucosides; Hesperidin; Hypertension; Male; NADPH Oxidases; Nitrates; Nitric Oxide Synthase Type III; Oxidative Stress; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Vasodilation

Candesartan has been reported to produce nitric oxide (NO) and to decrease oxidative stress in animal studies. We investigated candesartan's effect on the production of NO and oxidative stress as well as on carotid intima-media thickness (IMT) in hypertensive patients. One-hundred age-matched hypertensive patients were enrolled into an angiotensin II receptor blocker (ARB) group (n=50) or a non-ARB group (n=50). The ARB group was treated with candesartan 8 mg and, when needed, Ca channel blockers, angiotesin-converting enzyme (ACE) inhibitors, and/or beta-blockers. The non-ARB group was treated with drugs other than ARB. Carotid IMT was assessed by echocardiography before and 12 and 24 months after treatment. The urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an indicator of oxidative stress, and the serum levels of NOx, an indicator of NO, were measured. Blood pressure decreased to below 140/90 mmHg to the same extent in both groups. Carotid IMT decreased significantly in the ARB group, but not in the non-ARB group, at 12 and 24 months after treatment. The urine levels of 8-OHdG decreased significantly at 6 and 12 months after treatment in the ARB group but did not decrease in the non-ARB group. The serum levels of NOx increased significantly at 6 and 12 months after treatment in the ARB group but not in the non-ARB group. In conclusion, candesartan decreases carotid IMT by enhancing NO production and decreasing oxidative stress in patients with hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Carotid Arteries; Deoxyguanosine; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Tetrazoles; Tunica Intima; Tunica Media

The aim of this study is to investigate the effects of dietary supplementation with the Driselase-treated fraction (DF) of rice bran and ferulic acid (FA) on hypertension and glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP at 4 weeks of age were divided into three groups, and for 8 weeks were fed (1) a control diet based on AIN-93M, (2) a DF of rice bran-supplemented diet at 60 g/kg and (3) an FA-supplemented diet at 0.01 g/kg. Means and standard errors were calculated and the data were tested by one-way ANOVA followed by a least significance difference test. The results showed that both the DF and FA diets significantly improved hypertension as well as glucose tolerance, plasma nitric oxide (NOx), urinary 8-hydroxy-2'-deoxyguanosine and other parameters. In particular, compared to the FA diet, the DF diet produced a significant improvement in urinary NOx, hepatic triacylglycerol and several mRNA expressions of metabolic parameters involved in glucose and lipid metabolisms. The results of the metabolic syndrome-related parameters obtained from this study suggest that the DF diet is more effective than the FA diet.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Biomarkers; Blood Glucose; Coumaric Acids; Deoxyguanosine; Dietary Fiber; Fungal Proteins; Glucose Tolerance Test; Glycoside Hydrolases; Hypertension; Kidney; Lipid Metabolism; Liver; Male; Nitric Oxide; Oryza; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stroke

Accumulation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA is associated with mutagenesis and cell death. Little attention has been given to the biological significance of 8-oxo-dG accumulation in cardiovascular tissues during the different stage of hypertension and its prevention. We thus investigated the levels and localization of both 8-oxo-dG accumulation and expression of MTH1, which hydrolyzes 8-oxo-dGTP to prevent its incorporation into DNA, in the thoracic aorta prepared from stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wister-Kyoto rats (WKY), aged 5-32 weeks. HPLC-MS/MS analysis revealed that the levels of nuclear 8-oxo-dG in the aorta increased significantly in SHRSP, but not WKY, with aging. Immunohistochemical study revealed that both TUNEL reactivity and 8-oxo-dG immunoreactivity were increased in smooth muscle cells (SMC) and endothelial cells (EC) of the aorta with aging, and they exhibited similar distributions in serial sections. The number of 8-oxo-dG and TUNEL positive cells in EC, but not in SMC, was significantly higher in SHRSP than WKY at 32 weeks of age. In contrast, the expression levels of Mth1mRNA and MTH1 protein in the aorta were similarly decreased both in SHRSP and WKY with aging. However, the number of MTH1 expressing EC was remarkably increased in the older SHRSP compared to the younger ones or age-matched WKY. Hypertension significantly increased not only 8-oxo-dG accumulation but also the expression of MTH1 in EC of the aorta during aging. While accumulation of 8-oxo-dG in SMC of the aorta was slightly increased, the expression of MTH1 protein in SMC was rather decreased by hypertension. We thus suggest that MTH1 may protect EC in the aorta from the oxidative damage increased by hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; Cardiovascular Diseases; Deoxyguanosine; Disease Models, Animal; DNA Repair; DNA Repair Enzymes; Hypertension; Immunohistochemistry; Male; Mutagenesis; Phosphoric Monoester Hydrolases; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the detailed mechanism of reactive oxygen species (ROS) regulation is still unclear. This study examined the effect of high-salt diet on ROS production and expression of antioxidant enzymes in control and experimentally diabetic rats. Wistar fatty rats (WFR) as a type 2 diabetes mellitus model and Wistar lean rats (WLR) as a control were fed a normal-salt diet (NS) and high-salt diet (HS) from the age of 6 to 14 weeks. We then examined the blood pressure, urinary albumin excretion (UAE), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The expression of antioxidant enzymes including alpha-catalase (CAT), Cu-Zn superoxide dismutase (SOD), Mn SOD, and glutathione peroxidase (GPx) were analyzed in the glomeruli of the rats using Western blotting. The expression of NAD(P)H oxidase p47(phox) and NFkappaB p65 was evaluated using immunohistochemical staining. By 14 weeks of age, the WFR-HS group exhibited hypertension and markedly increased UAE. The level of 8-OHdG, a marker of oxidative damage, in the WFR-HS group was also higher than that in the WLR groups or WFR-NS group. The expression of alpha-CAT and Mn SOD proteins was significantly decreased in isolated glomeruli in the WFR-HS group. GPx and Cu-Zn SOD expression did not differ between the WFR and WLR groups. High expression of ROS and decreases in antioxidants were seen in the glomeruli of diabetic rats with hypertension, suggesting that oxidative stress may be involved in the development of DN.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; Blood Pressure; Blotting, Western; Body Weight; Deoxyguanosine; Diabetic Nephropathies; Disease Progression; Glucose Tolerance Test; Hypertension; Immunohistochemistry; Insulin; Kidney; Kidney Glomerulus; Male; NADPH Oxidases; Organ Size; Oxidative Stress; Rats; Rats, Inbred WKY; Rats, Zucker; Transcription Factor RelA

The present study was undertaken to identify whether inflammation or oxidative stress is the primary abnormality in the kidney in spontaneously hypertensive rats (SHR). Renal inflammation and oxidative stress were evaluated in 2- and 3-week-old prehypertensive SHR and age-matched genetically normotensive control Wistar-Kyoto (WKY) rats. Blood pressure was similar in WKY and SHR rats at 2 and 3 weeks, of age. Renal inflammation (macrophage and nuclear factor-kappaB) was elevated in SHR at 3 weeks, but not at 2 weeks, of age compared with age-matched WKY rats. Renal oxidative stress (nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and p47phox) was also clearly elevated in 3-week-old SHR compared with age-matched WKY rats. Additionally, NADPH oxidase subunit p47phox was found elevated in 2-week-old SHR compared to age-matched WKY rats. Moreover, antioxidant (N-acetyl-L-cysteine and Tempol) treatment reduced renal inflammation in prehypertensive SHR. We therefore conclude that the oxidative stress appears before inflammation as a primary abnormality in the kidney in prehypertensive SHR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Age Factors; Animals; Antioxidants; Blood Pressure; Cyclic N-Oxides; Deoxyguanosine; Disease Models, Animal; Disease Progression; DNA Damage; Glutathione; Hypertension; Kidney Cortex; Male; NADPH Oxidases; Nephritis; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spin Labels; Tyrosine

The potential use of oxidative stress products as disease markers and progression is an important aspect of biomedical research. In the present study, the quantification of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) concentration has been used to express the oxidation status of hypertensive subjects. 8-oxo-dG has been simultaneously isolated and assayed in nuclear (nDNA) and mitochondrial DNA (mtDNA). In addition, oxidative stress of mononuclear cells has been estimated by means of GSH and GSSG levels and GSSG/GSH ratio in hypertensive subjects before and after antihypertensive treatment. It is shown that oxidative stress decreases significantly in hypertensive patients after treatment the effect being accompanied by reduction of their blood pressure. A significant correlation is observed comparing the yield of urine 8-oxo-dG and that isolated from mitochondria DNA. Moreover, urinary excretion of 8-oxo-dG also correlates with the GSSG/GSH ratio of cells.. urine 8-oxo-dG assay is a good marker for monitoring oxidative stress changes in hypertensives.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cell Nucleus; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA, Mitochondrial; Female; Glutathione; Glutathione Disulfide; Humans; Hypertension; Male; Oxidative Stress

High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks).. A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG.. The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group.. This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Antibodies, Monoclonal; Deoxyguanosine; Disease Models, Animal; DNA; Femur Head; Femur Head Necrosis; Glucocorticoids; Hypertension; Immunohistochemistry; Oxidative Stress; Rats; Rats, Inbred SHR; Risk Factors; Severity of Illness Index

Monocyte adhesion to arterial endothelial cells is the initial step in atherosclerosis. Whereas angiotensin II is known to elicit leukocyte adhesion, it is not clear whether blockade of the angiotensin II receptor signaling reduces monocyte adhesion to endothelial cells beyond its antihypertensive action. This study compared the effect of two different antihypertensive drugs on monocyte adhesion to thoracic aorta endothelium in spontaneously hypertensive rats (SHR): the angiotensin II receptor blocker, valsartan (20 mg . kg(-1) . day(-1)) and the vasodilator, hydralazine (0.75 mg . kg(-1) . day(-1)). The effects were quantitated in vivo using an enface method that optimizes the observation of endothelial surfaces after immunohistochemical staining for CD68. Both agents significantly and comparably reduced blood pressure over 4-week treatment course. Both valsartan and hydralazine profoundly reduced monocyte adhesion compared with nontreated controls, with valsartan having a modestly more reductive effect. Both agents also reduced the intima and medial thickening with valsartan reducing the mean thickness modestly more than hydralazine. Our data confirms that the reduction of blood pressure is effective method to reduce monocyte adhesion. Also, our date demonstrates that valsartan has a modest beneficial effect on monocyte adhesion to endothelial cells and arterial intima-medial vessel thickening beyond its action as an antihypertensive agent.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Aorta; Atherosclerosis; Blood Pressure; Cell Adhesion; Deoxyguanosine; Endothelial Cells; Hydralazine; Hypertension; Male; Monocytes; Rats; Rats, Inbred SHR; Tetrazoles; Tunica Intima; Tunica Media; Valine; Valsartan

The present study was undertaken to investigate the redox status in the retina of an experimental model that combines hypertension and diabetes. Spontaneously hypertensive rats (SHR) and their control Wystar Kyoto (WKY) rats were rendered diabetic and, after 20 days, the rats were sacrificed and the retinas collected. The superoxide production was higher in diabetic than in control WKY (p < 0.03) and SHR rats showed elevated superoxide production compared with WKY groups (p < 0.009). The glutathione antioxidant system was diminished only in diabetic SHR (p < 0.04). Tirosyne nitration was higher in diabetic WKY and control SHR compared with control WKY (p < 0.03), and further increment was observed in diabetic SHR (p < 0.02). The DNA damage estimated by immunohystochemistry for 8-OHdG was higher in control SHR than in WKY, mainly in diabetic SHR (p < 0.0001). Hypertension aggravates oxidative-induced cytotoxicity in diabetic retina due to increasing of superoxide production and impairment of antioxidative system.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Deoxyguanosine; Diabetic Retinopathy; DNA Damage; Glutathione; Hypertension; Male; Nitrogen; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxide Dismutase; Tyrosine

Effect of dietary supplementation of two types of rice bran fraction on blood pressure (BP), lipid profile, and glucose metabolism in stroke-prone spontaneously hypertensive rats was studied. Male 4-week-old rats were divided into one group fed the AIN-93M-based control (C) diet and two groups fed diet supplemented with 60 g/kg of Driselase and ethanol fractions (DF and EF, respectively) of rice bran. After 8 weeks feeding, the BP decreased in the DF and EF groups in comparison with the C group (p < 0.01). Plasma ACE inhibitory activity, BUN, BUN/creatinine ratio, albumin, triglyceride, and glucose levels were lower in the DF and EF groups than in the C group (p < 0.01). Plasma nitric oxide and urinary 8-hydroxy-2'-deoxyguanosine levels were lower in the DF and EF groups than in the C group (p < 0.01). Rice bran fractions appear to have a beneficial dietary component that improves hypertension, hyperlipidemia, and hyperglycemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Blood Pressure; Catechin; Deoxyguanosine; Diet; Ethanol; Fungal Proteins; Gallic Acid; Glycoside Hydrolases; Hypertension; Lipids; Male; Nitric Oxide; Oryza; Rats; Rats, Inbred SHR; Stroke

It is known that renal nitric oxide (NO) is an important controller of urinary sodium excretion. A defect in the kidney's NO system could cause salt-sensitive hypertension. Since it has been demonstrated that doxorubicin binds to the reductase domain of endothelial NO synthase (eNOS) and generates superoxide in vitro, we tested our hypothesis that a high-sodium diet would upregulate the expression of eNOS and enhance oxidative stress in the kidney of doxorubicin-treated rats, resulting in a facilitation of hypertension. At 4 weeks after treatment with doxorubicin in Sprague-Dawley rats, the systolic blood pressure significantly increased only in the high-sodium diet group. The expressions of eNOS protein in the renal cortex and medulla were significantly higher in high-sodium groups than in normal-sodium groups, regardless of doxorubicin treatment. In rats treated with doxorubicin, a biomarker of oxidative damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunohistological staining of renal tissues showed strong staining of the proximal and distal tubules. In particular, rats with doxorubicin in the high-sodium diet group demonstrated a significant increase in urinary exertion of 8-OHdG as well as more prominently stained tubules against 8-OHdG antibody, but markedly lower urinary NO(x) excretion than in rats without doxorubicin, even than in the untreated, low-sodium group. In conclusion, these results indicate that the oxidative stress induced by doxorubicin impairs NO production in the kidney. As such, doxorubicin treatment appears to contribute to the development of salt-sensitive hypertension through reductive activation of upregulated eNOS by a high-sodium diet instead of NO production.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antibiotics, Antineoplastic; Blood Pressure; Deoxyguanosine; Doxorubicin; Food-Drug Interactions; Hypertension; Immunoenzyme Techniques; Kidney; Male; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sodium, Dietary; Up-Regulation

Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have anti-inflammatory and hypoglycemic activities. The aim of this study was to determine the effects of CRA on metabolic risk factors including obesity, hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with oxidative stress and inflammation, all of which are characteristic of the SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six-week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14 weeks. Treatment with CRA lowered blood pressure, which was elevated in control animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks. CRA treatment resulted in decreases in the levels of the oxidative stress markers thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and 59%, respectively, after 2 weeks. CRA treatment also reduced the levels of myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%, respectively, after 10 weeks, and tended to decrease the levels of high sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However, CRA had no effect on weight gain or hyperglycemia. These results demonstrate that CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress as well as the inflammatory state in SHR-cp rats. This implies that CRA can be beneficial for preventing atherosclerosis-related diseases that are an increasing health care problem worldwide.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Deoxyguanosine; Disease Models, Animal; Fatty Acids, Nonesterified; Hypertension; Inflammation; Insulin; Male; Metabolic Syndrome; Molecular Structure; Musa; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Inbred SHR; Thiobarbituric Acid Reactive Substances; Triglycerides; Triterpenes; Tyrosine

Oxidative stress is at play in the progression of chronic renal failure (CRF) and in the genesis of atherosclerosis. The aim of the present study was to evaluate the factors that might influence the oxidative-antioxidative balance in patients on hemodialysis. The study group consisted of 71 hemodialysis patients due to CRF. Sixteen healthy subjects constituted a control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), C-reactive protein (CRP), and the blood lipid profile were measured in both groups. The results showed significantly higher mean levels of both 8-OHdG and CRP in the hemodialysis patients compared with that in the control subjects. The highest level of 8-OHdG was found in the subgroups of the patients with CRF primarily caused by diabetes (16.4 ng/ml) and with hypertensive nephropathy (15.8 ng/ml). More than a 2.5-fold higher level of 8-OHdG in the hemodialysis patients compared with the control subjects points to the presence of intensive oxidative stress in the patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; C-Reactive Protein; Deoxyguanosine; Diabetes Complications; Glomerulonephritis; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Nephritis, Interstitial; Oxidative Stress; Renal Dialysis

Oxidative stress has been proposed as important in the pathogenesis of hypertension. Measurement of 8-iso prostaglandin F2alpha (8-ISO) is introduced for evaluating oxidative stress in vivo. 8-ISO is the major urinary metabolite of F2-isoprostanes and is formed nonenzymatically from the attack of superoxide radicals on arachidonic acid. We examined the oxidative stress level in the Dahl salt-sensitive (Dahl-S) rats and the Dahl salt-resistant (Dahl-R) rats. Dahl-S and Dahl-R rats were fed either a high salt diet (8% NaCl; HS) or low salt diet (0.3% NaCl; LS) for 3 weeks, and systolic blood pressure (SBP) and 24-hr urinary excretion of 8-ISO (U-8-ISO) were measured. In Dahl-S rats, the high salt diet induced hypertension (139 +/- 3 mmHg in LS versus 186 +/- 2 mmHg in HS, p < .05) and significantly increased the U-8-ISO (24.9 +/- 3.6 ng/24 hr in LS versus 63.2 +/- 14.6 ng/24 hr in HS, p < .05). No significant difference in blood pressure or U-8-ISO was observed between high-salt and low-salt treated Dahl-R rats. U-8-ISO concentration was correlated with SBP in all four experimental groups (r = 0.866). Moreover, urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), which is one of the most commonly used markers for evaluation of oxidative stress, was higher in Dahl-S-8% rats than in Dahl-S-0.3% rats (136.1 +/- 48.4 ng/24 hr in LS versus 322.8 +/- 46.7 ng/24 hr in HS, p < .05), and U-8-OHdG was correlated with SBP (r = 0.681) in Dahl-S rats. These results suggest oxygen radicals are involved in the pathogenesis of hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; Blood Pressure; Body Weight; Deoxyguanosine; Dinoprost; Heart Rate; Hypertension; Male; Oxidative Stress; Rats; Rats, Inbred Dahl

This study analyzed whether hypertension induced by N(omega)-nitro-l-arginine methyl ester (L-NAME) is associated with dysregulation of the main antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic administration of tempol ameliorates this hypertension.. Four groups of male Wistar rats were used: 1) control rats; 2) rats treated with L-NAME (35 mg/100 mL in drinking fluid); 3) rats treated with tempol (18 mg/100 mL in drinking fluid); and 4) rats treated with L-NAME plus tempol. All treatments were maintained for 6 weeks. Body weight, systolic blood pressure (BP) determined by the tail-cuff method, and heart rate were measured once per week. At the end of the experimental period, direct BP and morphologic, metabolic, plasma, and renal variables were measured. Enzymatic activities were measured in the kidney (cortex and medulla) and heart (right and left ventricles).. Rats with L-NAME-induced hypertension showed increased copper-zinc (Cu-Zn) SOD activity in the renal cortex and medulla and the left and right ventricles, which was reduced by tempol administration. The manganese (Mn) SOD activity was increased by L-NAME and reduced by tempol in the renal cortex but was unchanged in other tissues. Catalase activity was not affected by L-NAME or tempol treatments in any tissue. Both GPX and GR activities were increased by L-NAME and reduced by tempol in the renal cortex and medulla but were not affected in the ventricles. Tempol reduced BP and total urinary excretion of 8-hydroxy-2'-deoxyguanosine in L-NAME-treated animals but did not affect either variable in controls.. We conclude that L-NAME-induced hypertension is associated with an upregulation of antioxidant SOD, GPX, and GR activities. Moreover, the results indicate that tempol attenuates hypertension on nitric oxide-deficient rats and that oxidative stress participates in the established phase of this type of hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Biomarkers; Blood Pressure; Catalase; Cyclic N-Oxides; Deoxyguanosine; Disease Models, Animal; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Glutathione Peroxidase; Glutathione Reductase; Heart Rate; Heart Ventricles; Hypertension; Kidney Cortex; Kidney Medulla; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidative Stress; Oxidoreductases; Rats; Rats, Wistar; Spectrophotometry; Spin Labels; Superoxide Dismutase

Oxygen-free radicals and other oxygen/nitrogen species are constantly generated in the human body. Most are intercepted by antioxidant defences and perform useful metabolic roles, whereas others escape to damage biomolecules like DNA, lipids and proteins. Garlic has been shown to contain antioxidant phytochemicals that prevent oxidative damage. These include unique water-soluble organosulphur compounds, lipid-soluble organosulphur compounds and flavonoids. Therefore, in the present study, we have tried to explore the antioxidant effect of garlic supplementation on oxidative stress-induced DNA damage, nitric oxide (NO) and superoxide generation and on the total antioxidant status (TAS) in patients of essential hypertension (EH). Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls (Group II) were enrolled in the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were taken at the start of the study, i.e. 0 day, and thereafter 2 months follow-up. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipids, lipid peroxidation (MDA), NO and antioxidant vitamins A, E and C were determined. A moderate decline in blood pressure (BP) and a significant reduction in 8-OHdG, NO levels and lipid peroxidation were observed in Group I subjects with GP supplementation. Further, a significant increase in vitamin levels and TAS was also observed in this group as compared to the control subjects. These findings point out the beneficial effects of garlic supplementation in reducing blood pressure and counteracting oxidative stress, and thereby, offering cardioprotection in essential hypertensives.

Topics: 8-Hydroxy-2'-Deoxyguanosine; alpha-Tocopherol; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Cell Survival; Clinical Trials as Topic; Deoxyguanosine; Dietary Supplements; DNA Damage; Double-Blind Method; Garlic; Humans; Hypertension; Leukocytes, Mononuclear; Lipid Peroxidation; Lipids; Lipoproteins; Luminescent Measurements; Nitrites; Oxidation-Reduction; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Time Factors; Vitamin A

As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we analyzed the redox (reduction/oxidation) status in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative stress-induced DNA damage, and protein carbonylation, a marker for oxidation status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP compared with WKY. The expression of redox regulating protein, thioredoxin (TRX), estimated by immunohistochemistry and western blot, and expression of TRX gene estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR and SHRSP compared with WKY. Induction of TRX was impaired after angiotension II treatment in peripheral blood mononuclear cells isolated from SHR and SHRSP compared with those isolated from WKY. Although previous reports have shown that TRX is induced by a variety of oxidative stress in tissues, the present study shows the impaired induction of TRX in tissues from genetically hypertensive rats despite the relative increment of oxidative stress. Redox imbalance in essential organs may play a crucial role in the development and pathogenesis of hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensin II; Animals; Blotting, Western; Deoxyguanosine; Disease Models, Animal; Gene Expression Regulation; Hypertension; Immunohistochemistry; Monocytes; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thioredoxins

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Deoxyguanosine; Dioxoles; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Lignans; Rats; Rats, Inbred SHR; Stroke; Vitamin E

The objective was to study oxidative status, antioxidant activities, and reactive oxygen species byproducts in whole blood and mononuclear peripherals cells and their relationship with blood pressure. Sixty-six hypertensive patients and 16 normotensive volunteers as a control group were studied. In both, whole blood and peripheral mononuclear cells oxidized/reduced glutathione ratio and malondialdehyde was significantly higher, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly lower in hypertensive patients when compared with normal subjects. The content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and mitochondrial deoxyribonucleoproteins of hypertensive subjects was also significantly higher than that of the normotensive control subjects. No differences in these measurements were found among hypertensive subjects grouped in tertiles of 24-hour average mean blood pressure or between "white-coat" and established hypertensive subjects. Furthermore, no relationship was observed between the average of 24-hour mean blood pressure and oxidized/reduced glutathione ratio, reactive oxygen species byproducts, malondialdehide, or genomic 8-oxo-2'-deoxyguanosine. In whole blood and in mononuclear cells from hypertensive subjects, there was an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms that appeared to be independent of the blood pressure values.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Blood Pressure; Catalase; Deoxyguanosine; DNA; DNA, Mitochondrial; Female; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Humans; Hypertension; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase

To clarify the mechanism of involvement of oxidative stress in hypertensives, we investigated the relationship between the marker of oxidative DNA damage, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cardiovascular risk factors, such as hypertension and serum glycosylated hemoglobin (HbA1c), among Tanzanians aged 46-58 years who were not on antihypertensive medication.. Sixty subjects (males/females, 28/ 32) were selected randomly from the subjects who completed a 24h urine collection in our epidemiological study at Dar es Salaam, Tanzania in 1998. The subjects were divided into two groups, hypertensive subjects (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or =90 mmHg) and normotensive subjects (SBP < 140 mmHg and DBP < 90 mmHg) or hyperglycemic subjects (HbA1c > or = 6.0%) and normoglycemic subjects (HbA1c < 6.0%). Biological markers from urine and blood were analyzed centrally in the WHO Collaborating Center.. The mean levels of HbA1c and 8-OHdG were significantly higher in the hypertensive subjects than in the normotensive subjects (P < 0.05). Urinary 8-OHdG was significantly higher in hyperglycemic subjects than in normoglycemic subjects. HbA1c was positively correlated with the 24-h urinary 8-OHdG excretions (r= 0.698, P < 0.0001).. These findings suggest oxidative DNA damage is increased in hypertensive subjects, and there is a positive correlation between the level of blood glucose estimated as HbA1c and oxidative DNA damage. Hyperglycemia related to insulin resistance in hypertension in Tanzania is associated with increased urinary 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Cardiovascular Diseases; Circadian Rhythm; Deoxyguanosine; DNA Damage; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Male; Middle Aged; Oxidative Stress; Risk Factors; Tanzania

8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage. Pentosidine is a biomarker of glycoxidation reaction. In this study, we investigated relationships among 8-OHdG, pentosidine and age.. We determined the urinary concentrations of 8-OHdG and pentosidine in adults with mild hypercholesterolemia or/and mild hypertension (hypercholesterolemia group, n = 31; hypertension group, n = 25; hypercholesterolemia and hypertension group, n = 7).. The strength of the relationship between 8-OHdG and age was the same as that between pentosidine and age (the correlation coefficient between 8-OHdG and age was 0.33, pentosidine and age was 0.37). In addition, there was a positive and significant correlation between 8-OHdG and pentosidine. On the other hand, mean values of 8-OHdG and pentosidine showed no significant difference among the three groups.. The results of the present study indicate that both 8-OHdG and pentosidine levels increase similarly in degenerative pathologic conditions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Arginine; Deoxyguanosine; DNA Damage; Female; Glycation End Products, Advanced; Humans; Hypercholesterolemia; Hypertension; Lysine; Male; Middle Aged; Oxidative Stress

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Blood Vessels; Body Weight; Cerebrovascular Circulation; Cerebrovascular Disorders; Deoxyguanosine; Dioxoles; Disease Susceptibility; Drug Combinations; Genetic Predisposition to Disease; Hypertension; Lignans; Male; Microcirculation; Rats; Rats, Inbred SHR; Stroke; Thrombosis; Vasomotor System; Vitamin E

Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Deoxyguanosine; Female; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Organ Size; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sex Factors; Tanzania; Vitamin E