Biomedical subjects

Trevor A Mori

Publications and source records attributed to Trevor A Mori.

At least 19 recordsLinked to original sources

PubMed2026

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans↗

PubMed2006

A lifestyle program for treated hypertensives improved health-related behaviors and cardiovascular risk factors, a randomized controlled trial.

OBJECTIVE: To assess effects of a cognitively based program on health-related behaviors and cardiovascular risk factors in overweight drug-treated hypertensives. STUDY DESIGN AND SETTING: In a clinical trials center, volunteers, recruited by advertisement, were randomized to usual care (N=118) or to a 4-month program (N=123) incorporating weight loss; a low-sodium diet, high in fruit, vegetables, and fish; and increased physical activity. Diet, physical activity, weight, blood lipids, glucose, and insulin were measured at 4 and 16 months. RESULTS: Ninety-eight usual care and 106 program participants completed the 4-month assessment; 90 and 102, respectively, completed follow-up. Using intention-to-treat analysis, relative to usual care, net changes with the program at 4 months were as follows: dietary fat (-2.6% energy; P<0.001); sodium (-290mg/d; P=0.004); energy (-313mJ/d; P=0.005); fish (+2.1 serves/wk; P<0.001); vegetables (+3.0 serves/wk; P<0.001); physical activity (+37min/wk; P=0.004); weight (-2.8kg; P<0.001); waist girth (-3.1cm; P<0.001); total cholesterol (-0.2mmol/L; P=0.017); and triacylglycerols (-0.12mmol/L; P=0.002). One year later, net changes included dietary fat (-2.2% energy; P<0.001); sodium (-150mg/d; P=0.029); fish (+2.0 serves/wk; P<0.001); vegetables (+4.3 serves/wk; P<0.001); weight (-2.5kg; P=0.001); waist girth (-3.1cm; P<0.001); high-density lipoprotein cholesterol (+0.03mmol/L; P=0.031). CONCLUSION: Improvements in behaviors and risk factors, several maintained long term, suggest the potential for long-term benefits in hypertensives.

Adult↗

PubMed2006

Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.

Animals↗

PubMed2006

n -- 3 fatty acid supplementation during pregnancy in women with allergic disease: effects on blood pressure, and maternal and fetal lipids.

n--3 Fatty acids derived from fish oil reduce plasma triacylglycerols (triglycerides) and increase HDL-C (high-density lipoprotein cholesterol); however, the effect of n--3 fatty acid supplementation during pregnancy, a hyperlipidaemic state, remains unknown. We took the opportunity to investigate maternal lipid levels and blood pressure during and after pregnancy, and fetal lipid levels at birth, in a study that aimed primarily to examine the effect of fish oil supplementation during pregnancy on immune function in infants born to women with allergic disease. Eighty-three pregnant women who had allergic disease, but were otherwise healthy, completed the study. They were randomly allocated to receive fish oil or olive oil capsules, taken as 4 g/day, from 20 weeks of pregnancy until delivery. Compared with olive oil, fish oil supplementation did not alter triacylglycerols, total cholesterol, LDL-C (low-density lipoprotein cholesterol) or HDL-C during or after pregnancy. There was also no effect of fish oil on cord blood triacylglycerols, total cholesterol, LDL-C or HDL-C. Fish oil supplementation during pregnancy did not alter maternal blood pressure during or after pregnancy. The effects of fish oil on lipids and blood pressure in non-pregnant individuals appear to be lost when it is administered during pregnancy.

Adult↗

PubMed2006

Lupin-enriched bread increases satiety and reduces energy intake acutely.

BACKGROUND: Protein and fiber may be important determinants of satiety. Lupin kernel flour is a novel food ingredient that is rich in protein and fiber. OBJECTIVE: The objective was to investigate the effects of lupin kernel flour-enriched bread (LB) on satiety and energy intake in humans. DESIGN: Two randomized controlled crossover trials were performed to compare the acute effects of LB with those of white bread (WB). In study 1, the subjects (n = 16) completed 4 treatments 1 wk apart: WB breakfast (as toast) and WB lunch (as sandwiches), WB breakfast and LB lunch, LB breakfast and WB lunch, and LB breakfast and LB lunch. Energy intake at all breakfast meals was matched (1655 kJ), and ad libitum energy intake at lunch, 3 h after breakfast, was measured. In study 2, the subjects (n = 17) completed 2 treatments 1 wk apart: WB breakfast and LB breakfast (each 1655 kJ). Blood samples were taken at baseline and at regular intervals for 3 h after breakfast. RESULTS: In study 1, the LB breakfast resulted in significantly higher self-reported satiety (P < 0.001) and lower energy intake (kJ) at lunch (-488; 95% CI: -798, -178) than did the WB breakfast. The LB lunch resulted in a significantly lower within-meal energy intake (kJ) at lunch (-1028; 95% CI: -1338, -727) than did the WB lunch. In study 2, compared with the WB breakfast, the LB breakfast significantly altered the 3-h postmeal plasma ghrelin response (P = 0.04) and resulted in significantly lower mean 3-h plasma ghrelin concentrations (P = 0.009). CONCLUSION: A novel food enriched in protein and fiber derived from lupin kernel flour significantly influences energy intake acutely.

Area Under Curve↗

PubMed2006

The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans.

PURPOSE OF REVIEW: This review details the independent effects of purified eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. We report data from the recent literature and our own controlled clinical trials which compared the independent effects of these fatty acids in individuals at increased risk of cardiovascular disease, namely overweight hyperlipidaemic men and treated-hypertensive, type 2 diabetic men and women. We discuss the biological effects of these fatty acids and the potential mechanisms through which they may affect cardiovascular disease risk factors. RECENT FINDINGS: A cardioprotective effect for omega3 fatty acids is supported by prospective studies demonstrating an inverse association between fish intake and coronary heart disease mortality. Data from secondary prevention trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. Clinical trials and experimental studies have shown that omega3 fatty acids have many other potentially important antiatherogenic and antithrombotic effects. Omega-3 fatty acids lower blood pressure and heart rate, improve dyslipidaemia, reduce inflammation, and improve vascular and platelet function. These favourable effects have until recently been primarily attributed to the omega3 fatty acid eicosapentaenoic acid, which is present in large amounts in fish oil. Controlled studies in humans now demonstrate that docosahexaenoic acid, although often present in lower quantities, has equally important anti-arrhythmic, anti-thrombotic and anti-atherogenic effects. SUMMARY: Available evidence strongly suggests that eicosapentaenoic acid and docosahexaenoic acid have differing haemodynamic and anti-atherogenic properties. The effects of the two fatty acids may also differ depending on the target population.

Cardiovascular Diseases↗

PubMed2006

Omega-3 fatty acids and hypertension in humans.

1. Population studies and clinical trials provide compelling evidence that omega-3 (omega3) fatty acids have cardioprotective effects. The strongest evidence is from DART and GISSI-P, two secondary prevention trials in patients with previous myocardial infarctions. Data from these trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. 2. Evidence suggests that w3 fatty acids may also provide protection against stroke, particularly ischaemic stroke. 3. The cardioprotective effects of omega3 fatty acids relate to improvements in blood pressure, cardiac function, arterial compliance and vascular function, as well as improved lipid metabolism, antiplatelet and anti-inflammatory effects. 4. Clinical trials in humans have shown that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have different haemodynamic properties. Docosahexaenoic acid may be more favourable in lowering blood pressure and heart rate, as well as improving vascular function. However, the effects of EPA and DHA may also differ depending on the target population.

Antihypertensive Agents↗

PubMed2005

Prevention of programmed hyperleptinemia and hypertension by postnatal dietary omega-3 fatty acids.

Fetal programming is now recognized as a key determinant of the adult phenotype, with major implications for adult-onset diseases including hypertension. Two mediators of fetal programming are maternal nutrition and fetal glucocorticoid exposure. Recent studies show that postnatal dietary manipulations can exacerbate programming effects, but whether programming effects can be attenuated by postnatal dietary manipulations, and thus provide a possible therapeutic strategy, is unknown. In this study, we tested the hypothesis that a postnatal diet enriched with long-chain omega-3 fatty acids attenuates programmed hyperleptinemia and hypertension. Pregnant rats were treated with dexamethasone (Dex) from d 13 to term, and offspring were cross-fostered to mothers on either a standard diet or a diet high in omega-3 fatty acids and remained on these diets postweaning. Maternal Dex reduced birthweight and delayed the onset of puberty in offspring. Hyperleptinemia (associated with elevated leptin mRNA expression in adipose tissue) and hypertension were evident in offspring by 6 months of age in Dex-exposed animals consuming a standard diet, but these effects were completely blocked by a high omega-3 diet. These results demonstrate for the first time that manipulation of postnatal diet can limit adverse outcomes of fetal programming, with programmed hyperleptinemia and hypertension prevented by a postnatal diet enriched with omega-3 fatty acids. This raises the possibility that dietary supplementation with omega-3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

Animals↗

PubMed2005

Processes involved in the site-specific effect of probucol on atherosclerosis in apolipoprotein E gene knockout mice.

OBJECTIVE: To elucidate processes by which the antioxidant probucol increases lesion size at the aortic sinus and decreases atherosclerosis at more distal sites in apolipoprotein E-deficient (apoE(-/-)) mice. METHODS AND RESULTS: Male apoE(-/-) mice were fed high-fat chow with 1% (w/w) probucol or without (controls) for 6 months, before aortic sinus, arch, and descending aorta were analyzed separately for lesion size and composition. Compared with control, probucol significantly increased lesion size by 33% at the sinus, but it inhibited atherosclerosis at the descending aorta by 94%. Sites where atherosclerosis was inhibited contained substantially fewer macrophages, less lipids (cholesterol and cholesteryl esters), and endogenous antioxidant (alpha-tocopherol), but not oxidized lipids, and the extent to which probucol metabolism occurred was increased. Compared with control, aortic sinus lesions of probucol mice contained a substantially increased content of extracellular matrix, but decreased total cell and macrophage density, comparable levels of lipids and alpha-tocopherol, and decreased concentrations of oxidized lipids (cholesteryl ester hydroperoxides, F2-isoprostanes, and 7-ketocholesterol). CONCLUSIONS: Probucol affects atherosclerosis in apoE(-/-) mice independent of the accumulation of arterial lipid oxidation products, thereby dissociating the 2 processes. Rather, probucol exerts antiinflammatory activity by decreasing accumulation of macrophages in lesions, and it promotes a more stable lesion composition at the aortic sinus.

Animals↗

PubMed2005

Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy.

In many diseases, including progressive renal disorders, tissue injury and pathological intracellular signaling events are dependent on oxidative stress. Glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that is highly expressed in the kidney and removes peroxides and peroxynitrite that can cause renal damage. Therefore, we examined whether this abundant renal antioxidant enzyme limits renal damage during the development of type 1 diabetic nephropathy. Wild-type (Gpx1+/+) and deficient (Gpx1-/-) mice were made diabetic by intraperitoneal injection of streptozotocin (100 mg/kg) on 2 consecutive days. Diabetic Gpx1+/+ and -/- mice with equivalent blood glucose levels (23 +/- 4 mM) were selected and examined after 4 mo of diabetes. Compared with normal mice, diabetic Gpx1+/+ and -/- mice had a two- to threefold increase in urine albumin excretion at 2 and 4 mo of diabetes. At 4 mo, diabetic Gpx1+/+ and -/- mice had equivalent levels of oxidative renal injury (increased kidney reactive oxygen species, kidney lipid peroxidation, urine isoprostanes, kidney deposition of advanced glycoxidation, and nitrosylation end products) and a similar degree of glomerular damage (hypertrophy, hypercellularity, sclerosis), tubular injury (apoptosis and vimentin expression), and renal fibrosis (myofibroblasts, collagen, TGF-beta excretion). A lack of Gpx1 was not compensated for by increased levels of catalase or other Gpx isoforms in diabetic kidneys. Contrary to expectations, this study showed that the high level of Gpx1 expressed in the kidney is not protective against the development of renal oxidative stress and nephropathy in a model of type 1 diabetes.

Animals↗

PubMed2005

Apocynin but not allopurinol prevents and reverses adrenocorticotropic hormone-induced hypertension in the rat.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. METHODS: Male Sprague-Dawley rats were divided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F2-isoprostane concentrations. Results were expressed as mean+/-SEM. RESULTS: ACTH increased SBP (P<.001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142+/-3 ACTH, 120+/-4 mm Hg apocynin+ACTH, P'<0.001) and reversed ACTH-induced hypertension (133+/-4 to 118+/-5 mm Hg, P<.05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9+/-1.0 vs 8.2+/-0.8 nmol/L, P<.01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. CONCLUSIONS: Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.

Acetophenones↗

PubMed2005

The use of novel foods enriched with long-chain n-3 fatty acids to increase dietary intake: a comparison of methodologies assessing nutrient intake.

OBJECTIVE: To evaluate the effect of consuming a variety of foods enriched in long-chain n-3 fatty acids in low fish eaters. DESIGN: Evaluation of reported dietary intakes in a 6-month, double-blind, randomized, controlled parallel design trial. SUBJECTS/SETTING: Eighty-five men and women with overweight and mildly elevated triglyceride levels who have a low habitual intake of fish. INTERVENTION: Subjects were randomized to consume foods either enriched in long-chain n-3 fats or control foods (not enriched). Subjects were asked to consume eight portions per day (equivalent to approximately 1 g/day long-chain n-3 fatty acid if randomized to the intervention). MAIN OUTCOME MEASURE: Reported energy, macronutrient, and fatty acid intakes were measured by diet history, 3-day food records, and body weight. STATISTICAL ANALYSES: Repeated measures analysis of variance, Kruskall-Wallis test, Pearson's correlation coefficient, and Bland-Altman plots were conducted. RESULTS: The two groups did not differ in mean dietary intake of long-chain n-3 fatty acid intake at baseline (258 mg and 313 mg for the intervention and control groups, respectively). At 6 months the intervention group members increased their intake of long-chain n-3 fats 4.5-fold compared with baseline and with the control group (P<.001). The data from the diet histories correlated well with the food records for all reported macronutrient and fatty acid values. Food pattern analysis showed that milk (13.8%), cereal (12.1%), and bread (11.3%) contributed the most to the overall long-chain n-3 fatty acid intake in the intervention group. CONCLUSIONS: This long-term study in free-living subjects indicates that population intakes of long-chain n-3 fatty acids could be substantially increased through the availability of a variety of n-3 fatty acid-enriched processed foods.

Adult↗

PubMed2005

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

OBJECTIVE: To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. DESIGN: Randomized controlled trial. SETTING: Research studies unit. PARTICIPANTS: Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). INTERVENTION: A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. MAIN OUTCOME MEASURES: Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. RESULTS: Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P < 0.01). At follow-up, changes in the two groups were not significantly different (4.1/1.3 +/- 1.1/1.0 mmHg in controls; 2.5/-0.1 +/- 1.1/0.8 mmHg in the programme group; P = 0.73). At 4 months, drug withdrawal differed significantly between the groups (P = 0.038) in men (control 44%; programme 66%) but not in women (65 and 64%, respectively; P = 0.964). At follow-up, sex-related differences were not significant, and 41% in the control group and 43% in the programme group maintained drug-withdrawal status. With the programme, net weight loss was 3.3 kg (P < 0.001) at 4 months and 3.0 kg (P < 0.001) at follow-up; respective net decreases in waist girth were 3.3 cm (P < 0.001) and 3.5 cm (P < 0.001). CONCLUSIONS: A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

Antihypertensive Agents↗

PubMed2004

Induced sputum 8-isoprostane concentrations in inflammatory airway diseases.

Induced sputum 8-iso-prostaglandin F(2alpha) (PGF(2alpha)) concentrations may be a useful marker of oxidative stress in airways disease. This study examines oxidative stress (measured by 8-iso-PGF(2alpha)) in airway disease according to disease type (asthma and bronchiectasis), disease activity (stable and acute asthma), and disease pattern (intermittent, mild, moderate, and severe persistent asthma). We compared subjects with stable asthma (n = 71) and bronchiectasis (n = 23) with healthy control subjects (n = 29). Another group of patients with asthma (n = 39) were assessed during and after acute exacerbation. Induced sputum 8-iso-PGF(2alpha) concentrations were validated and found to be elevated in subjects with stable asthma and bronchiectasis versus control subjects (median [interquartile range] 216 [103-389] and 698 [264-1,613] ng/L vs. 123 [41-290] ng/L, p < 0.001) and increased as clinical asthma pattern worsened (intermittent 115 [42-153], mild persistent 116 [89-229] ng/L, moderate persistent 183 [110-317] ng/L, severe persistent 387 [102-587] ng/L; p = 0.010). Sputum 8-iso-PGF(2alpha) concentrations were elevated during acute asthma and decreased with recovery (458 [227-950] ng/L vs. 214 [148-304] ng/L, p = 0.0002). We conclude that 8-iso-PGF(2alpha) is involved in the pathophysiology of inflammatory airway diseases, being related to disease type, pattern, and activity. Analysis of 8-iso-PGF(2alpha) concentrations in induced sputum provides a useful tool for monitoring oxidative stress and investigating strategies aimed at reducing oxidative stress in airways disease.

Adult↗

PubMed2004

Oxidative stress in human hypertension: association with antihypertensive treatment, gender, nutrition, and lifestyle.

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F2-isoprostanes (p <.05). Self-reported alcohol intake and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls.

Antihypertensive Agents↗

PubMed2004

Omega-3 fatty acids and inflammation.

Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

Animals↗

PubMed2004

The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat.

BACKGROUND: Many forms of hypertension are associated with increased oxidative stress. This study investigated the effects of Tempol, a superoxide scavenger, on prevention and reversal of hypertension induced by the synthetic glucocorticoid dexamethasone (Dex) in the rat. METHODS: Male Sprague-Dawley rats (n = 10 in each group) were treated with saline or Dex (10 microg/kg/day subcutaneously) for 13 days. Tempol (1 mmol/L) was given in drinking water from 4 days before treatment (prevention) or from treatment day 8 (T8) (reversal). Systolic blood pressure (SBP) was measured by the tail-cuff method. Plasma F(2)-isoprostane concentrations were measured as a highly specific marker of oxidative stress. Thymus weight was measured as a marker of glucocorticoid activity. RESULTS: Dex treatment increased SBP (122 +/- 5 to 136 +/- 3 mm Hg, P <.05) and plasma F(2)-isoprostane concentrations (P =.005). Tempol alone did not alter SBP, but Tempol pretreatment prevented Dex-induced hypertension compared with that in rats treated with Dex alone (128 +/- 4 and 144 +/- 7 mm Hg respectively, P' <.05). Tempol partially reversed Dex-induced hypertension (122 +/- 5 and 136 +/- 3 mm Hg, respectively, P' =.057). Thymus weight was decreased in Dex-treated rats compared with saline treated rats (157 +/- 10 saline and 105 +/- 6 mg/100 g body weight Dex, P <.0005). Tempol affect neither thymus weight nor F(2)-isoprostane concentrations. CONCLUSIONS: Chronic Dex treatment increased SBP and tended to increase oxidative stress shown as increased plasma F(2)-isoprostane concentrations. Tempol prevented and partially reversed Dex-induced hypertension, independent of improvement in systemic oxidative stress measured by F(2)-isoprostane concentrations.

Animals↗

PubMed2004

Fish oil supplementation in pregnancy lowers F2-isoprostanes in neonates at high risk of atopy.

The anti-inflammatory properties of n-3 polyunsaturated fatty acids (n-3 PUFA) have suggested a potential role of these nutrients in dietary modification for prevention of allergic disease in early life. As oxidative stress is known to modify antigen presenting cell (APC) signalling and resulting immune responses, we examined the effects of maternal n-3 PUFA supplementation in pregnancy on markers of oxidative stress and APC function in neonates at high risk of allergy. Eighty-three pregnant atopic women were randomised to receive 4 g daily of either fish oil (n = 40) or olive oil (n = 43) capsules in a controlled trial from 20 weeks gestation until delivery. Plasma (cord blood) and urinary F2-isoprostanes were measured as markers of lipid peroxidation. Cord erythrocyte fatty acids and markers of APC function (HLA-DR expression and cytokine responses) were measured and related to levels of plasma F2-isoprostanes. Maternal fish oil supplementation lowered plasma (p < 0.0001) and urinary (p = 0.06) F2-isoprostanes. HLA-DR expression on APC was not different between the groups. In multiple regression analysis, 28.8% of the variance in plasma F2-isoprostanes was explained by positive relationships with erythrocyte arachidonic acid (AA) and monocyte HLA-DR expression and a negative relationship with erythrocyte eicosapentaenoic acid (EPA). This study shows that maternal supplementation with fish oil can attenuate neonatal lipid peroxidation. Clinical follow-up of these infants will help to determine if there are sustained effects on postnatal oxidative stress and expression of allergic disease.

Adult↗