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)

S-nitrosoalbumin (SNO-Alb) is a major reservoir of releasable nitric oxide (NO) in plasma. In preeclampsia, a pregnancy-specific disorder associated with endothelial dysfunction, we previously found significant elevations in plasma SNO-Alb concentrations and decreased plasma ascorbate (Asc) levels. This increased SNO-Alb may result from low-plasma Asc if Asc, along with transition metals (eg, copper [Cu]) are necessary for release of NO from S-nitrosothiols. We propose that vasodilator effects of SNO-Alb, mediated by release of NO, are fully realized only when Asc/Cu availability is sufficient. Relaxation responses to SNO-Alb or the control reduced human serum albumin (SH-Alb), and responses to pooled plasma from normal or preeclamptic pregnancies were examined in isolated mouse arteries. Arteries preconstricted with phenylephrine were exposed to SNO-Alb or SH-Alb at physiologically relevant concentrations. When free Cu was added in excess (10 mumol/L), NO release was not dependent on Asc. However, when Cu was added at lower (physiological) levels, NO release was dependent on Asc. The addition of Asc and Cu to SNO-Alb stimulated vasodilatory responses in isolated arteries >90%, whereas no change in the SH-Alb (5%) response was observed. Preeclampsia plasma with higher levels of SNO-Alb caused arteries to relax 44.1+/-4.7%, whereas normal pregnancy plasma caused 11.9+/-4.2% relaxation (P=0.007). These data indicate that SNO-Alb alone or in plasma can act as a potent vasodilator, and that sufficient Asc/Cu promotes this action. We suggest that the higher circulating levels of SNO-Alb, in women with preeclampsia, reflect a deficiency in Asc/Cu-mediated release of NO from SNO-Alb.
Hypertension 2005 Jan
PMID:S-nitrosoalbumin-mediated relaxation is enhanced by ascorbate and copper: effects in pregnancy and preeclampsia plasma. 1555 88

Trace element deficiencies have been documented to play an important role in determination of the fetal outcome. Pregnant women in developing countries have been reported to consume diets with a lower density of minerals and vitamins. Deficiencies of trace elements like zinc, copper and magnesium have been implicated in various reproductive events like infertility, pregnancy wastage, congenital anomalies, pregnancy induced hypertension, placental abruption, premature rupture of membranes, still births and low birth weight. The present review article highlights the important of role played by zinc, copper and magnesium during pregnancy and its outcome. The role of individual trace elements and in combination with other trace elements has not been completely documented. There is a need to undertake further studies in this field.
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PMID:Role of trace elements zinc, copper and magnesium during pregnancy and its outcome. 1557 21

Moderate ethanol consumption is known to reduce the risk of cardiovascular diseases; however, chronic high dose ethanol ingestion causes cardiovascular injuries including hypertension. The dose response of ethanol-induced hypertension and associated oxidative stress response has not been well established. This study investigated the dose response of ethanol on blood pressure (BP), nitric oxide (NO) and antioxidants in the plasma of the rat. Male Fisher rats (200-250 g) were divided into five groups of six animals each and treated as follows: (1) control (5% sucrose, orally) daily for 12 weeks; (2) 20-30% ethanol (1 g kg-1, orally) daily for 12 weeks; (3) 20-30% ethanol (2 g kg-1, orally) daily for 12 weeks; (4) 20-30% ethanol (4 g kg-1, orally) daily for 12 weeks; (5) 20-30% ethanol (6 g kg-1, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week through tail-cuff method. The animals were sacrificed 12 weeks after treatments and blood was collected and analyzed. Systolic and mean BP were slightly decreased with 1 g kg-1 dose but significantly elevated with 2, 4 and 6 g kg-1 doses 7-12 weeks after ethanol ingestion. Whereas diastolic BP was significantly elevated with 4 and 6 g kg-1 doses 8-12 weeks after ethanol ingestion. Blood alcohol levels were significantly elevated with 4 and 6 g kg-1 dose of ethanol for 12 weeks. Ethanol dose-dependency increased plasma malondialdehyde (MDA) and protein carbonyl levels, while nitric oxide (NO), ratio of reduced to oxidized glutathione (GSH/GSSG) and antioxidant enzymes: copper/zinc-superoxide dismutase (CuZn-SOD) and manganese (Mn)-SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were decreased 12 weeks post-treatment. The data suggested that ethanol induces hypertension at higher doses by depleting NO and antioxidants and increasing oxidative tissue injury in rats.
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PMID:Dose response of alcohol-induced changes in BP, nitric oxide and antioxidants in rat plasma. 1568 47

We studied the effect of VIBOVITmama (Polfa Kutno S.A.) supplementation on the course of pregnancy duration, delivery and puerperium and also the status of zinc, copper and selenium in the blood of matched maternal-cord pairs. Healthy pregnant women (n=138) were divided by a double blinded trial into a test group taking vitamin and mineral supplementation containing 15 mg of zinc, 2 mg of copper and 20 microg of selenium and a control group taking placebo. Course of pregnancy, delivery and puerperium were analyzed, as well as concentration of bioelements in the blood serum of pregnant women in the I, II, and II trimester and in umbilical cord blood of their children. In the study group we noted fewer by 1.45% cases of pregnancy induced hypertension and a much higher rate of natural deliveries (75%) in comparison to the control group (53%). During pregnancy in the supplemented group a 1% increase of zinc serum concentration was found. In the control group zinc concentration decreased by 7% (p < 0.005). Insignificant differences in serum concentration of copper and selenium was observed between the study group and controls. In umbilical cord blood the differences in the concentration of the above microelements were also insignificant. The results allow for the statement that VIBOVITmama supplementation stabilizes the zinc, copper and selenium levels in blood of pregnant women without the risk of overdosing, especially with reference to selenium.
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PMID:[Effect of vitamin-mineral supplementation on the status of some microelements in pregnant women]. 1579 17

Eleven metal elements in niuhuang jiangya wan, including sodium, calcium, magnesium, potassium, iron, chromium, manganese, nickel, cadmium, copper and zinc, were determined by flame atomic absorption spectrophotometer. The results showed that there are rich metal elements in niuhuang jiangya wan and provided useful data for discussing the relation between trace elemtnts in niuhuang jiangya wan and cure for high blood pressure.
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PMID:[Determination of 11 metal elements in niuhuang jiangya wan by atomic absorption spectrophotometer]. 1581 77

Recent studies have suggested that the calcium antagonists have an antiatherogenic antioxidant property. The effects of the calcium antagonists on reactive oxygen species (ROS)-related enzymes, however, remain unknown. We hypothesized that the calcium antagonists inhibit oxidative stress in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) through the ROS-scavenging enzymes known as superoxide dismutases (SODs). Male 12-week-old Wister-Kyoto rats (WKY) and SHRSP were used for the study. SHRSP were randomized and treated for 6 weeks with a vehicle, amlodipine (5 mg/kg/day), or enalapril (10 mg/kg/day). NAD(P)H oxidase activity was measured by a luminescence assay, and SOD activity was measured spectrophotometrically. Protein expressions were analyzed by immunoblots. Both drugs showed equipotent effects on systolic blood pressure, left ventricular hypertrophy and fibrosis, the wall-to-lumen ratio, the manganese SOD activity, ROS, and the endothelial NO synthase expression in the SHRSP hearts. Furthermore, amlodipine significantly restored copper/zinc-containing SOD (Cu/ZnSOD) expression and its activity in SHRSP hearts to a level equal to that of WKY more effectively than did enalapril (p <0.05), whereas enalapril downregulated NAD(P)H oxidase activity more than did amlodipine (p <0.05) in the SHRSP hearts. Furthermore, amlodipine restored Cu/ZnSOD expression and its activity in SHRSP hearts to a level equal to that in WKY hearts, and this restoration was significantly more effective than that by enalapril (p <0.05); on the other hand, enalapril induced a greater downregulation of NAD(P)H oxidase activity in SHRSP hearts than did amlodipine (p <0.05). Thus, amlodipine may inhibit vascular remodeling and oxidative stress in the SHRSP heart by efficiently upregulating Cu/ZnSOD, suggesting that the calcium antagonist may exhibit an antiatherogenic antioxidative action beyond blood-pressure lowering through the restoration of Cu/ZnSOD activity in the heart in cases of hypertension.
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PMID:Calcium antagonist reduces oxidative stress by upregulating Cu/Zn superoxide dismutase in stroke-prone spontaneously hypertensive rats. 1582 70

The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 microg/g w.w. was 17 times greater than average liver Cd load (1.1 microg/g w.w.). In contrast, average kidney cortex Pb load of 0.09 microg/g w.w. was two times lower than liver Pb load of 0.19 microg/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Pb loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r=-0.39, P=0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r=0.37, P=0.02) whereas kidney CYP4F2 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r=0.40, P=0.02). These findings suggest that Cd may be an inducer of renal CYP4F2 and hepatic CYP2E1 and that increased renal CYP4F2 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism.
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PMID:Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1. 1599 32

The aim of the study was to verify the hypothesis if copper could influence the activity of sodium-transporting systems in erythrocyte membrane that could be related to essential hypertension. The examined group of patients consisted of 15 men with hypertension. The control group was 11 healthy male volunteers. The Na+/H+ exchanger (NHE) activity in erythrocytes was determined according to Orlov et al. The activity of transporting systems (ATP-Na+/K+; co-Na+/K+/Cl-; ex-Na+/Li+; free Na+ and K+ outflow [Na+, K+-outflow]) was determined according to Garay's method. The concentration of copper in plasma was assessed using atomic absorption spectrometry. The activity of ATP-Na+/K+ (micromol/L red blood cells [RBCs]/h) in hypertensive patients was 2231.5 +/- 657.6 vs 1750.5 +/- 291 in the control (p < 0.05), the activity of co-Na+/K+/Cl- (micromol/L RBCs/h) in hypertensives was 171.3 +/- 77.9 vs 150.7 +/- 53.9 in the control (NS). Na+-outflow (micromol/L RBCs/h) in hypertensives was 118.3 +/- 51.6 vs 113.3 +/- 24.4 in the control (NS). The K+-outflow (micromol/L RBCs/h) in hypertensives was 1361.7 +/- 545.4 vs 1035.6 +/- 188.3 in the control (NS). The activity of ex-Na+/Li+ (micromol/L RBCs/h) in hypertensive patients was 266.1 +/- 76.1 vs 204.1 +/- 71.6 in the control (p < 0.05). NHE activity (mmol/L RBCs/h) in hypertensives was 9.7 +/- 2.96 vs 7.7 +/- 1.33 in the control (p < 0.05). In hypertensive patients, negative correlation was found between the activity of Na+/K+/Cl- co-transport and plasma copper concentration (Rs = -0.579, p < 0.05) and between the activity of ex-Na+/Li+ and plasma copper concentration (Rs = -0.508, p < 0.05). Plasma copper concentration significantly influences the activity of sodium transporting systems in erythrocyte membrane. Copper supplementation could be expected to provide therapeutic benefits for hypertensive patients.
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PMID:Copper modifies the activity of sodium-transporting systems in erythrocyte membrane in patients with essential hypertension. 1617 Feb 19

Tin is commonly used as a coating on copper kitchen appliances, and "tinsmithing" as a trade is common in many non-Western countries, where cooking utensils are re-tinned when the cooking surface wears thin. Tinsmiths, or "tinkers," are commonly exposed to the following fumes during their work: stannic [tin(IV)] oxide, ammonium chloride, and hydrochloric acid. In this study we assessed workers from tinsmith workshops of our province for signs, symptoms, and laboratory evidence of cardiac end-organ damage. Between June 2002 and March 2003, researchers went to the main tinsmith workshop area of our province to interview tinsmiths in their workplaces and to gather addresses of their "traveling tinker" colleagues, who work with portable equipment. All workers were interviewed and underwent a complete physical examination, blood testing for lipid parameters, and echocardiography. Twenty-six tin workers (mean age 49+/- 10 y) and 25 control patients (convenience sample of hospital employees) were included in the study. Tobacco use, incidence of hypertension, and serum lipid parameters were not significantly different between the two groups (p < .05). The differences in myocardial performance index, systolic function, and mitral flow A velocity were also nonsignificant. However, the mitral inflow E velocity in the tinsmiths was significantly less than in controls (0.71+/- 0.1 vs. 0.95+/- 0.1 m/s, p < .001). The mitral deceleration time was also much longer in the tinsmith group (216+/- 71 ms vs. 143+/- 14 ms, p < .001). Eleven of the tinkers (23%) were found to have aortic valve sclerosis (severe in one, moderate in another, mild in the other nine), but aortic valve sclerosis was found in none of the control subjects. One tinsmith was found to have three-vessel coronary disease on angiogram. Another tinker with "myocarditis" in the past, and slow flow on angiography, had normalization of his cardiac tests after refraining from tin exposure for 6 mo. Thus, occupational exposure to heavy tin fumes is associated with left ventricle diastolic dysfunction and sclerosis of the aortic valve. Tin workers should minimize their exposure to tin fumes, and physicians should monitor tinsmiths closely for signs of heart disease.
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PMID:Cardiac damage secondary to occupational exposure to tin vapor. 1632 1

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.
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PMID:Future direction of renal positron emission tomography. 1635 95


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