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)

Rats were made hypertensive by the administration of the nitric oxide synthase inhibitor nitro-L-arginine (LNA, 2.74 mmol/L) in drinking water for 7 d. Hearts from hemodynamically assessed animals were analyzed for lipid peroxidation (LPO), gamma-glutamylcysteine-synthetase (gamma-GCS), glutathione disulfide reductase (GR), glutathione peroxidase (GSHPx), catalase (CAT), superoxide dismutase (SOD), and total radical trapping potential (TRAP) activities. LNA treatment increased the mean arterial blood pressure by 46% and the heart rate by 22% without changing plasma renin activity. LNA treatment resulted in a 30% increase in LPO. gamma-GCS was reduced by 48% and GR by 36% in the cardiac tissue of hypertensive rats as compared to controls. The activity of nonselenium GSHPx was reduced by 27%, and selenium-dependent GSHPx activity in the heart was not affected by LNA treatment. In hypertensive rats, SOD activity was increased by 16%, and CAT was decreased by 46%. TRAP was lower (27%) in the myocardium of hypertensive rats than in that of controls. These data suggest that LNA-induced hypertension is associated with increased myocardial oxidative stress.
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PMID:Myocardial oxidative stress and antioxidants in hypertension as a result of nitric oxide synthase inhibition. 1221 96

Although it may be 20 years before a male contraceptive is marketed, researchers continue to explore various options. Part of the difficulty with male contraception is the fact that the oral contraceptives were so successful in women that they cornered the market. Another problem is that it is easier to control one egg per month than hundreds of millions of sperm cells each day. Another is that it is more expensive to do research on male than on female rats since the males require separate cages. The physiologic targets for male birth control are 1) the process of spermatogenesis, 2) the process of sperm maturation, and 3) the process of capacitation. The substance gossypol, which suppresses sperm without affecting androgen levels, has been the subject of male contraceptive research in the US since the 1970s. Clinical trials of gossypol are planned by a collaborative groups of investigators from developing countries. Research has also continued for more than 20 years on compounds to alter male hormone levels. The use of one such compound, testosterone enanthate, required weekly injections, so current research is centered on finding a more marketable product, such as a 3-month injectable that uses testosterone buciclate. The combination of testosterone enanthate with cyproterone acetate is also showing promise in achieving complete azoospermia in trials in men. The dosing schedule makes this regimen unmarketable, however. Protocols have also been completed for a clinical trial using two implanted rods to deliver a GnRH analog and a specially developed androgen. Work is also proceeding on the development of a GnRH vaccine and on a vaccine specific only to follicle-stimulating hormone. Other avenues of research are focusing on nifedipine, a drug used to treat high blood pressure, on mifepristone (RU-486) which temporarily blocks calcium, and on etoprine, which suppresses rapidly dividing sperm cells. Research has halted on two compounds that protect cells from oxidative damage (superoxide dismutase and glutathione peroxidase) because of the potential damage to sperm DNA, which could cause early miscarriage or birth defects.
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PMID:Pills, shots, implants, vaccines: can the elusive sperm be reined in? Male contraceptive research extremely slow, but promising. 1229 Jul 17

Nitric oxide (NO) has a role in the etiopathogenesis of hypertension. Relaxation of vascular smooth muscles is failed when NO production is reduced leading to increased vascular peripheral resistance. N sup omega nitro-L-arginine methyl ester (L-NAME) is one of the inhibitors of NO production. The aim of this study was to investigate oxidant-antioxidant systems of renal tissue in rats with hypertension induced by L-NAME. Rats were divided into three groups: control group and study groups treated with 100 or 500 mg/l L-NAME in drinking water for 15 days. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and NO were studied in the renal tissue after hypertension induction. Arterial blood pressure was increased in both L- NAME groups. CAT activity of 500-mg L-NAME group was higher than control. GSH-Px activity of 500-mg L-NAME group was decreased compared with 100-mg ones. NO level was lower in 500-mg L-NAME group than control. MDA levels in both L-NAME groups were decreased compared with control. In conclusion, hypertension was induced with oral L-NAME treatment. Increased CAT activity was compensated with decreased GSH-Px activity in 500-mg L-NAME group. Both study groups were protected from lipid peroxidation with NO inhibition.
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PMID:Renal antioxidant status in rats with hypertension induced by N sup omega nitro-L-arginine methyl ester. 1242 22

Antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) are components of an organism's mechanisms for combating oxidative stress which is generated in normal metabolism and which may also be a reaction in response to external stimuli. This review identifies the general significance of antioxidant enzymes in health and disease, and some of the diseases that are now believed to have oxidative stress as a component. A discussion is then presented of the molecular mechanisms by which antioxidant enzyme expression is controlled at the transcriptional and post-transcriptional levels. The final sections of the review highlight the effects of exercise and hypertension on antioxidant enzyme expression in a number of different tissues, and the possibilities for future studies in these areas are discussed.
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PMID:Antioxidant enzyme expression in health and disease: effects of exercise and hypertension. 1245 78

An influence of intermittent hypoxia (IH) on antioxidant enzymes activity was investigated in 42 patients, aged 48.2 +/- 1.8 years, with 1-2-nd stage of dyscirculatory encephalopathy (DE) in the presence of I-II stage of arterial hypertension (AH). Patients with arterial pressure below 145/85 mmHg receiving basic antihypertensive drugs treatment were included in the study. Before IH, the patients showed increased total oxidant activity (TOA) as well as concentration of thiobarbituric acid reactive substances (TBRS) in blood plasma and reduced activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP) in erythrocytes comparing to control group (14 healthy subjects). In 27 patients, it was combined with increased peak systolic and peak diastolic blood flow rate in middle cerebral artery according to Doppler examination. After 10 days hypoxia training (60 min daily atmospheric air breathing alternated with 9-10 V% O2 hypoxic mixture breathing), TOA and TBRS were decreased by 39% and 25% respectively, whereas enzymes activity was increased as follows: SOD--by 29%; CAT--by 18%; GP--by 38%. The treatment resulted in reduction of peak systolic and peak diastolic blood flow rate in the meddle cerebral artery, decrease of frequency of headache episodes and in improvement of nighttime sleep and short-term memory. The results demonstrate a possibility for correction of oxidative homeostasis disturbances in patients with DE on the background of AH and can be beneficial for DE prevention and treatment.
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PMID:[Intermittent hypoxia in the treatment of dyscirculatory encephalopathy]. 1249 93

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.
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PMID:Circulating biomarkers of oxidative stress in complicated pregnancies. 1259 16

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.
Hypertension 2003 May
PMID:Antioxidant activities and oxidative stress byproducts in human hypertension. 1475 30

Cardiovascular (systolic and diastolic blood pressure, heart rate), antihyperlipidemic (tryglycerides, total cholesterol and lipoprotein fractions), antioxidant (glutathione peroxidase--GPx, and superoxide dismutase--SOD), diuretic/saluretic and hypoglycemic activity of 98% pure oleanolic (OA) and ursolic (UA) acid were studied in Dahl salt-sensitive (DSS), insulin resistant rat model of genetic hypertension. Both OA and UA displayed low toxicity, with LC50 0.10 and 0.95 mg/ml, respectively. Although both triterpenoids did not have direct hypotensive effect, after 6-week application in a daily dose 60 mg/kg b.w., i.p., they prevented the development of severe hypertension. The antihypertensive effect was attributed to their potent diuretic-natriuretic-saluretic activity; direct cardiac effect (heart rate decrease by 34% and 32%, respectively); antihyperlipidemic (more than two times decrease of LDL and triglycerides); antioxidant (GPx increase by 12% and 10%, respectively; SOD increase by 12% and 22%, respectively), and hypoglycemic (blood glucose decrease by 20% and 50%, respectively) effects on the DSS rats. Except for the antihyperlipidemic effects, the other described above in vivo antihypertensive effects of OA and UA are reported for the first time and the underlying mechanisms are currently under investigation.
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PMID:Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. 1272 63

A positive family history of coronary heart disease (CHD) is one of the most predictive risk factors of CHD. Many children with increased risk of CHD because of their positive family history of CHD do not present other risk factors, such as altered serum lipid profile. Oxidative stress plays an important part in the pathogenesis of atherosclerosis. Serum antioxidants and intracellular enzymatic antioxidants composed mainly of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase counterbalance oxidative stress. Diminished activity of this system may lead to accelerated progression of atherosclerosis. The aim of this study was to assess the activity of CAT, GSH-Px, SOD and glutathione reductase in children with a family history of premature CHD who did not present any other major risk factors of CHD (diabetes, obesity, dyslipidaemia or hypertension). Twenty-two healthy children from high-risk families, selected according to the National Cholesterol Education Program definition, were enrolled in the study. The control group comprised 18 children without a family history of CHD. All the children were healthy and had been screened for hyperlipidaemia, diabetes, hypertension and obesity prior to the study. The erythrocyte activity of CAT, GSH-Px, SOD and glutathione reductase was assessed. Children at high risk of CHD had a statistically significant lower level of GSH-Px and CAT activity than the children in the control group. There were no statistically significant differences in the activity of SOD and glutathione reductase.
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PMID:Activity of antioxidant enzymes in children from families at high risk of premature coronary heart disease. 1275 97

The study investigated whether the amelioration of endothelial dysfunction by candesartan (2 mg.kg-1.day-1; 10 wk) in spontaneously hypertensive rats (SHR) was associated with modification of hepatic redox system. Systolic arterial pressure (SAP) was higher (P < 0.05) in SHR than in Wistar-Kyoto rats (WKY) and was reduced (P < 0.05) by candesartan in both strains. Acetylcholine (ACh) relaxations were smaller (P < 0.05) and contractions induced by ACh + NG-nitro-l-arginine methyl ester (l-NAME) were greater (P < 0.05) in SHR than in WKY. Treatment with candesartan enhanced (P < 0.05) ACh relaxations in SHR and reduced (P < 0.05) ACh + l-NAME contractions in both strains. Expression of aortic endothelial nitric oxide synthase (eNOS) mRNA was similar in WKY and SHR, and candesartan increased (P < 0.05) it in both strains. Aortic mRNA expression of the subunit p22phox of NAD(P)H oxidase was higher (P < 0.05) in SHR than in WKY. Treatment with candesartan reduced (P < 0.05) p22phox expression only in SHR. Malonyl dialdehyde (MDA) levels were higher (P < 0.05), and the ratio reduced/oxidized glutathione (GSH/GSSG) as well as glutathione peroxidase activity (GPx) were lower (P < 0.05) in liver homogenates from SHR than from WKY. Candesartan reduced (P < 0.05) MDA and increased (P < 0.05) GSH/GSSG ratio without affecting GPx. Vessel, lumen, and media areas were bigger (P < 0.05) in SHR than in WKY. Candesartan treatment reduced (P < 0.05) media area in SHR without affecting vessel or lumen area. The results suggest that hypertension is not only associated with elevation of vascular superoxide anions but with alterations of the hepatic redox system, where ANG II is clearly involved. The results further support the key role of ANG II via AT1 receptors for the functional and structural vascular alterations produced by hypertension.
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PMID:Effect of AT1 receptor blockade on hepatic redox status in SHR: possible relevance for endothelial function? 1277 56


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