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Query: UMLS:C0020538 (hypertension)
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Elevated fasting insulin concentrations and insulin resistance have been associated with non-insulin-dependent diabetes mellitus (NIDDM), obesity, atherosclerosis, and hypertension. Vitamin E supplementation in persons with and without NIDDM may be related to greater insulin sensitivity (SI). The cross-sectional associations of the intake of vitamins E and C with SI and insulin concentrations were evaluated among African American, Hispanic, and non-Hispanic white men and women with a wide spectrum of glucose tolerance included in the Insulin Resistance and Atherosclerosis Study (IRAS) (n = 1151). Insulin sensitivity was measured by minimal model analysis of a 12-sample, insulin-modified, frequently sampled intravenous glucose tolerance test. Nutrient intake (including vitamin supplement use) was assessed with a food-frequency questionnaire modified to include foods consumed by the three ethnic groups. Linear-regression models were used, including rank of SI and the log of fasting insulin as the outcome variables. Pearson correlation coefficients for vitamins E and C in relation to rank SI were r = 0.07 (P = 0.01) and r = 0.07 (P = 0.02), respectively. After adjustment for total energy and BMI these associations were no longer statistically significant and did not differ between ethnic groups. Results were similar when vitamins E and C were combined in categories of low and high antioxidant intake. Models replicated with log of fasting insulin as the outcome variable also did not produce significant associations with vitamins E or C. Thus, these cross-sectional analyses do not support the hypothesis of improved SI with increased intake of vitamins E and C.
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PMID:Insulin sensitivity and intake of vitamins E and C in African American, Hispanic, and non-Hispanic white men and women: the Insulin Resistance and Atherosclerosis Study (IRAS). 935 42

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.
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PMID:Nutrition and dietary supplements. 1051 85

We recently showed elevated reactive oxygen species (ROS), reduced urinary excretion of NO metabolites (NOx), and increased NO sequestration as nitrotyrosine in various tissues in rats with lead-induced hypertension. This study was designed to discern whether the reduction in urinary NOx in lead-induced hypertension is, in part, due to depressed NO synthase (NOS) expression. Male Sprague-Dawley rats were randomly assigned to a lead-treated group (given lead acetate, 100 ppm, in drinking water and regular rat chow), a group given lead and vitamin E-fortified chow, or a normal control group given either regular food and water or vitamin E-fortified food for 12 weeks. Tail blood pressure, urinary NOx excretion, plasma malondialdehyde (MDA), and endothelial and inducible NOS (eNOS and iNOS) isotypes in the aorta and kidney were measured. The lead-treated group exhibited a rise in blood pressure and plasma MDA concentration, a fall in urinary NOx excretion, and a paradoxical rise in vascular and renal tissue eNOS and iNOS expression. Vitamin E supplementation ameliorated hypertension, lowered plasma MDA concentration, and raised urinary NOx excretion while significantly lowering vascular, but not renal, tissue eNOS and iNOS expression. Vitamin E supplementation had no effect on either blood pressure, plasma MDA, or NOS expression in the control group. The study also revealed significant inhibition of NOS enzymatic activity by lead in cell-free preparations. In conclusion, lead-induced hypertension in this model was associated with a compensatory upregulation of renal and vascular eNOS and iNOS expression. This is, in part, due to ROS-mediated NO inactivation, lead-associated inhibition of NOS activity, and perhaps stimulatory actions of increased shear stress associated with hypertension.
Hypertension 1999 Oct
PMID:Nitric oxide synthase expression in the course of lead-induced hypertension. 1052 26

Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Glutathione, another natural antioxidant, may also be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus. Our group has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium levels (Mg([i])). Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions. To directly investigate the effects of vitamin E supplementation on insulin sensitivity in hypertension, in relation to the effects on circulating levels of reduced (GSH) and oxidized (GSSG) glutathione and on Mg([i]), we performed a 4-week, double-blind, randomized study of vitamin E administration (600 mg/d) versus placebo in 24 hypertensive patients and measured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/GSSG ratios, and Mg([i]) before and after intervention. The relationships among WBGD, GSH/GSSG, and Mg([i]) in both groups were evaluated. In hypertensive subjects, vitamin E administration significantly increased WBGD (25.56+/-0.61 to 31.75+/-0.53 micromol/kg of fat-free mass per minute; P<0.01), GSH/GSSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg([i]) (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01). In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r=0.58, P=0.047) and Mg([i]) (r=0.78, P=0.003). These data show a clinical link between vitamin E administration, cellular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further studies are needed to explore the cellular mechanism(s) of this association.
Hypertension 1999 Oct
PMID:Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. 1052 98

Vitamin E, the major lipid soluble plasma antioxidant, has been reported to be reduced in patients with coronary atherosclerosis. We have measured the levels of plasma alpha-tocopherol (the predominant form of plasma vitamin E) in 128 patients with different reported degrees of angina. Patients with mild to moderate angina (grades I or II (CSS score)) (n = 64), and patients with severe angina (grades III and IV) (n = 64) were recruited from Cardiology Clinics in the U. K. Healthy controls (n = 33) and patients with hyperlipidaemia (n = 28) were also recruited. The groups of patients with angina did not differ significantly for mean age (58 +/- 1.0 years vs. 59 +/- 1.0 years, respectively); sex distribution (the M:F ratio was 48 : 16 and 46 : 18 for the respective groups); or prevalence of smoking (12% vs. 9%), or hypertension (19% vs. 33%). Total cholesterol levels were higher in the group with severe angina (5.9 +/- 0.16 mmol/l vs. 5.3 +/- 0.13 mmol/l P < 0.05). Absolute levels of plasma vitamin E were not significantly different between the angina subgroups (12.9 +/- 0.40 mg/l for the mild-moderate angina group vs. 12.5 +/- 0.51 mg/l for the severely affected group), but were positively correlated with plasma cholesterol concentrations in each case (P < 0.001). The ratio between plasma vitamin E: total cholesterol was significantly lower in the patients with severe angina (mean 2.20 +/- 0.09 mg/mmol) vs. a mean value of 2.46 +/- 0. 08 mg/m mol in the mildly affected group (P < 0.05). The plasma vitamin E: total cholesterol ratio in patients with severe angina was also significantly lower (P < 0.05) compared to either healthy controls with comparable total cholesterol levels (n = 33), or hypercholesterolaemic subjects (n = 28) without symptomatic coronary disease (mean ratios were 2.69 +/- 0.40 mg/mmol and 2.74 +/- 0.68 mg/mmol, respectively). Vitamin E has previously been demonstrated to protect endothelial function in the presence of hypercholesterolaemia, possibly by preserving nitric oxide bio-activity. It also inhibits LDL oxidation. Hence, a high plasma vitamin E: total cholesterol ratio may be associated with an amelioration of angina.
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PMID:Cholesterol standardized plasma vitamin E levels are reduced in patients with severe angina pectoris. 1071 65

Vitamin E, a potent antioxidant, may play a role in preventing preeclampsia. Maternal blood samples were collected between 28 and 40 weeks' gestation from women with mild preeclampsia (n=17), women with severe preeclampsia (n=16) and the control group (n=15). This control group was consisted of 15 pregnant women without hypertension episode during their pregnancy. Vitamin E levels were significantly higher in normotensive pregnant women (1.00+/-0.20 mg/dL) than in those with mild (0.56+/-0.15 mg/dL) or severe (0.37+/-0.75 mg/dL) preeclampsia (P<0.001). In preeclamptic women, when systolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05), also when diastolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05). Measurement of vitamin E concentration in plasma may be useful as a prognostic marker of the likely development of preeclampsia.
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PMID:Maternal levels of vitamin E in normal and preeclamptic pregnancy. 1083 20

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
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PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

Oxidative modification of low-density lipoprotein (LDL) increases atherogenic potential to induce the accumulation of lipids and cells in the vascular wall. Previous studies reveal that hypertensive patients have a higher susceptibility to LDL oxidation. As animal models indicate that vitamin E protects LDL from oxidation, here we study the influence of vitamin E on the resistance of LDL to oxidation (lag time) in 47 subjects (31 normotensive, 16 hypertensive) before and after oral administration of vitamin E (400 IE) daily for two months. LDL was isolated and oxidised by incubation with copper ions. The time course of oxidation was measured by continuous photometric monitoring of diene formation at 234 nm. At the beginning of this study, normotensive subjects showed a lag time of 108 +/- 26 minutes and hypertensive patients a lag time of 85 +/- 24 minutes (P<0.05). Vitamin E caused a significant increase in the lag time in both groups: normotensive subjects 128 +/- 33, hypertensives patients 114 +/- 27 minutes (P<0.01). At completion of the study, lag times in both groups were similar (P=not significant). The data presented here suggests that vitamin E protects against the increased risk of vascular disease in patients with hypertension by reducing the susceptibility to oxidative modification of LDL. Vitamin E may therefore act as an inhibitor of atherogenesis.
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PMID:Vitamin E prevents extensive lipid peroxidation in patients with hypertension. 1268 Jun 23

Development and progression of end-organ damage in hypertension have been associated with increased oxidative stress. Superoxide anion accumulation has been reported in deoxycorticosterone acetate (DOCA)-salt hypertension, in which endothelin-1 plays an important role in cardiovascular damage. We hypothesized that blockade of ETA receptors in DOCA-salt rats would decrease oxidative stress. Both systolic blood pressure (SBP, 210+/-9 mm Hg; P<0.05) and vascular superoxide generation in vivo were increased in DOCA-salt (44.9+/-10.3% of ethidium bromide-positive nuclei; P<0.05) versus control uninephrectomized (UniNx) rats (118+/-3 mm Hg; 18.5+/-3%, respectively). In DOCA-salt rats, the ETA antagonist BMS 182874 (40 mg/kg per day PO) lowered SBP (170+/-4 versus UniNx, 120+/-3 mm Hg) and normalized superoxide production (21.7+/-6 versus UniNx, 11.9+/-7%). Vitamin E (200 mg/kg per day PO) decreased superoxide formation in DOCA-salt rats (18.8+/-7%) but did not alter SBP. Oxidative stress in nonstimulated circulating polymorphonuclear cells (PMNs) or in PMNs treated with zymosan, an inducer of superoxide release, was similar in DOCA-salt and UniNx groups. Superoxide formation by PMNs was unaffected by treatment with BMS 182874. Western blot analysis showed increased nitrotyrosine-containing proteins in mesenteric vessels from DOCA-salt compared with UniNX. Treatment with either BMS 182874 or vitamin E abolished the differences in vascular nitrotyrosine-containing proteins between DOCA-salt and UniNX. Maximal relaxation to acetylcholine was decreased in DOCA-salt aortas (75.8+/-4.2% versus UniNx, 95.4+/-1.9%, P<0.05). BMS 182874 treatment increased acetylcholine-induced relaxation in DOCA-salt aortas to 93.5+/-4.5%. These in vivo findings indicate that increased vascular superoxide production is associated with activation of the endothelin system through ETA receptors in DOCA-salt hypertension, in apparently blood pressure-independent fashion.
Hypertension 2003 Oct
PMID:ETA receptor blockade decreases vascular superoxide generation in DOCA-salt hypertension. 1291 63

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
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PMID:Anti-atherosclerotic effects of vitamin E--myth or reality? 1509 Feb 61


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