Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structural elucidation and mechanism of action of a potential component, LLU-alpha, of what is possibly a multifactorial complex known as "natriuretic hormone" was recently reported [Wechter, W.J. et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93: 6002-6007]. "Natriuretic hormone," a long-sought factor, is believed to regulate extracellular fluid volume and consequently be pathomimetic for hypertension, cirrhosis, congestive heart failure and other volume expanded states. The studies reported herein further characterize LLU-alpha. The precursor of the endogenous LLU-alpha was demonstrated to be gamma-tocopherol by radiolabeling studies. The pharmacokinetics of infused rac-LLU-alpha proved to be biphasic (half-lives: 12 min and 6 h). Specificity of the inhibition of the 70 pS potassium channel of the thick ascending limb of the loop of Henle was examined with the natural S-enantiomer being the most potent known inhibitor whereas the analogous alpha-tocopherol metabolite, rac-5-Me-LLU-alpha, showed no inhibition. Rac-LLU-alpha does not inhibit two isozymes of the Na+/K+-ATPase. LLU-alpha is natriuretic acting via inhibition of the 70 pS potassium channel and not Na+/K+-ATPase, the assumed mechanism of action of the "natriuretic hormone." LLU-alpha, a metabolite of a vitamin, if it were found to play a role in the regulation of extracellular fluid volume, would be the second example of a vitamin acting as a precursor for a hormone. Of considerable interest is the fact that this manuscript reports the first biological activity of gamma-tocopherol, a member of the vitamin E complex.
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PMID:Endogenous natriuretic factors 7: biospecificity of a natriuretic gamma-tocopherol metabolite LLU-alpha. 926 27

The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer. These dietary associations may explain in part the reduced rates of uterine cancer in Asian countries compared with those in the United States.
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PMID:Association of soy and fiber consumption with the risk of endometrial cancer. 927 Apr 8

Hypertension, hypercholesterolemia, atherosclerosis, and coronary heart disease are associated with abnormal endothelium-dependent, nitric oxide-mediated vasorelaxation. In rats, hypercholesterolemia in combination with deficiencies of vitamin E and selenium results in increased endogenous lipid oxidation and endothelial dysfunction. Two hydroxymetabolites of doxazosin, an alpha 1-adrenergic blocking antihypertensive agent, inhibit human lipid oxidation in vitro in a dose-dependent fashion. The present studies were performed to determine the effect of in vivo treatment with doxazosin on endothelial dysfunction in hypercholesterolemic/ antioxidant-deficient rats. Dahl rats were fed 1) a standard diet, 2) a high cholesterol (4%) diet, or 3) a high cholesterol, vitamin E- and selenium-deficient diet. A subgroup of animals in each group were administered doxazosin (3.5 mg/100 g/day) for 16 weeks. In the aortas, vascular relaxations induced by acetylcholine were significantly decreased (P < .05) in high cholesterol/antioxidant-deficient rats compared with normal and high cholesterol animals. Doxazosin treatment prevented the impairment in endothelium-dependent vascular relaxation in the high cholesterol/antioxidant-deficient group. Vasorelaxation in response to the exogenous nitric oxide donor diethylamine nanoate, which was significantly impaired (P < .05) in aortas from high cholesterol/antioxidant-deficient animals compared with normal and high cholesterol animals, was normalized in aortas from high cholesterol/ antioxidant-deficient animals that had received doxazosin. The antioxidant effect of doxazosin may have therapeutic implications in diseases associated with endothelial dysfunction linked to products of lipid oxidation.
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PMID:Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats. 939 45

Usage of antisclerotic diet with PUFA n-3 from vegetable or animal source in 326 patients with IHD, HL and HBP resulted in positive dynamic of clinical manifestation, blood lipids and coagulogramms of the patients. The favorable changes of membrane lipids and the decrease of intensity of lipid peroxidation was also revealed. The decrease of primary and secondary metabolites of lipid peroxidation could be a result of hypolipidemic effect of the diets and sufficient level of vitamin E. We suppose that vitamin A and b-carotene content of butter "Laplandia" had additional mild antioxidant influence.
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PMID:[Lipid peroxidation in patients with ischemic heart disease, hyperlipidemia and/or hypertension while polyunsaturated omega-3 fatty acids of plant and animal origin were in their diet]. 941 77

Between 1986 and 1991, 29,584 persons took part in a randomized nutritional intervention trial in Linxian, China, an area whose residents had chronically low intakes of several nutrients and high rates of esophageal and gastric cardia cancer as well as stroke. Using a one-half replicate of a 2(4) factorial design, we randomized individuals to one of eight groups which received combinations of four supplements: retinol and zinc (factor A); riboflavin and niacin (factor B); vitamin C and molybdenum (factor C); and beta-carotene, alpha-tocopherol (vitamin E), and selenium (factor D). Deaths that occurred during 5 years of supplementation were ascertained and classified according to cause. At the end of the supplementation period, we measured blood pressure readings and determined the prevalence of hypertension. Participants who received factor D had reductions in total mortality (9%) and total cancer mortality (13%). These individuals also had the largest reduction in stroke mortality (relative risk = 0.91; 95% confidence interval = 0.76-1.07). End-of-trial hypertension, however, was not less prevalent among those receiving factor D. Our findings contrast with the larger reductions in stroke death and hypertension found in a parallel trial of Linxian subjects with esophageal dysplasia who received a multivitamin/mineral supplement, suggesting an effect largely derived from nutrients other than those received in the present study.
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PMID:Do nutritional supplements lower the risk of stroke or hypertension? 943 Feb 58

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4+/-3.4 versus 10.2+/-3 units of relative fluorescence/mg LDL protein, P<.05), longer lag phase (54+/-10 versus 88+/-10 minutes, P<.05), lower propagation rate (8.2+/-2.5 versus 5.95+/-2.1 nmol diene/min per mg LDL cholesterol, P<.05), higher LDL vitamin E content (8.3+/-1.1 versus 10.1+/-1.8 nmol/mg LDL cholesterol, P<.05), and plasma vitamin C content (40+/-13 versus 57+9 micromol/L, P<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.
Hypertension 1998 Feb
PMID:Low-density lipoprotein oxidation and vitamins E and C in sustained and white-coat hypertension. 946 Dec 31

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. The purpose of this study was to explore the degree of oxidative stress in essential arterial hypertension (EAH). The study groups consisted of fifteen untreated EAH patients (WHO stages 1 and 2), aged 40 to 70 years, and fifteen, age and sex matched, normal controls. The levels of typical peroxidation products such as malondialdehyde and 4-hydroxyalkenals (with the LPO-586 test, Bioxytech), free radicals and other reactive oxygen metabolites (ROMs) (with the d-ROMs test, Diacron), vitamin E (with HPLC method) and total antioxidant capacity (with the TAS test, Randox) were determined in the plasma af all subjects. Compared to the control group EAH patients exhibited significantly higher ROMs levels (334.7 +/- 21.6 vs 249.2 +/- 23.3 Units, means values +/- S.E.M.), and of lipid peroxidation products (10.7 +/- 0.7 vs 8.09 +/- 0.9 nmol/ml). It must be noted that such increases were not observed in all EAH patients, but above all in those less young or with more severe hypertension. On the other hand no significant difference was found between EAH patients and normal controls as regards vitamin E concentration and total antioxidant capacity. These results suggest that EAH patients, in spite of their normal antioxidant defences, are more prone than normotensive subjects to oxidative stress because of an increased ROMs production. This could result in an inactivation of prostacyclin and NO, hence an enhancement of peripheral vascular resistance and an increase of hypertension. Another consequence might be an increased lipid peroxidation of low density lipoproteins, a condition which is known to be associated with accelerated atherosclerosis. The study of oxidant and antioxidant factors seems therefore useful in EAH patients in order to evaluate oxidative stress and to correct, if possible, the observed abnormalities with dietetic or pharmacologic therapy.
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PMID:[Reactive metabolites of oxygen, lipid peroxidation, total antioxidant capacity and vitamin E in essential arterial hypertension]. 949 52

We tested the hypothesis that oxidative stress, mediated by dietary vitamin E deprivation, would alter vascular function through the interaction of oxygen-derived free radicals and nitric oxide (NO). This interaction may play an important role in the vascular pathophysiology of many diseases associated with oxidative stress. Mesenteric arteries from control (n = 12) and vitamin E-deprived (n = 12) Sprague-Dawley rats were studied with a myograph. Superoxide dismutase, which scavenges superoxide anions, produced a significantly greater relaxation in the arteries from the vitamin E-deprived rats compared with the controls (P<.05). Superoxide dismutase and catalase produced results similar to superoxide dismutase alone. Pretreatment with an NO synthase inhibitor eliminated the superoxide dismutase-induced relaxation in arteries from both control and vitamin E-deprived rats. L-Arginine induced a greater relaxation in arteries of the vitamin E-deprived group (P<.05). Agonist-induced relaxation with methacholine was not altered by superoxide dismutase for either group of animals, indicating that stimulated release of NO was not influenced by superoxide anions. With the use of Western immunoblot analysis, nitrotyrosine residues were shown to be present in arteries from both the vitamin E-deprived and control rats, but the amount of nitrotyrosine observed was not different between the two groups. In summary, our data indicate that there is a greater inhibition of NO caused by superoxide anions in the vitamin E-deprived group. We speculate that in conditions of oxidative stress (reduced vitamin E levels), altered vascular function may be due to increased destruction of NO by oxygen-derived free radicals.
Hypertension 1998 Mar
PMID:Vascular function in the vitamin E-deprived rat: an interaction between nitric oxide and superoxide anions. 949 68

Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.
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PMID:Oxidative stress and lipids in diabetes: a role in endothelium vasodilator dysfunction? 954 38

Defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of nitric oxide (NO) or increased production of free radicals, mainly the superoxide anion, may facilitate the development of an arterial functional spasm. Although it has been shown that many antihypertensive drugs can normalise both the antioxidant activity and NO, the antioxidant effect of N-dicyclopropylmethyl-amino-2-oxazoline (S-3341), an alpha-adrenoreceptor agonist, has not been investigated. In this study we investigated the antioxidant and NO status in hypertensive patients and whether there was any effect of S-3341 on these parameters. Eleven patients with mild hypertension (mean systolic blood pressure 159.5 +/- 2.5 mmHg) were administered S-3341 (1 mg/day) for 4 weeks. Plasma vitamin E, nitrite-nitrate and MDA levels, and catalase activity, were measured both before and after treatment with S-3341. There was significant reduction in both mean systolic and diastolic blood pressure during the treatment. We found an increase in catalase activity (p < 0.05), a decrease in malondialdehyde (MDA) levels (p < 0.01) and an insignificant increase in vitamin E levels in hypertensive patients following the S-3341 treatment. We propose that S-3341 may prevent oxidant stress in hypertensive patients by inhibiting free-radical formation.
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PMID:Effect of N-dicyclopropylmethyl-amino-2-oxazoline (S-3341) on antioxidant status and nitric oxide in hypertensive patients. 970 98


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