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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary form of primary hyperaldosteronism that presents with hypokalemia and hypertension from childhood onward. GRA is characterized by the ectopic production of aldosterone in the cortisol-producing zona fasciculata under the regulation of adrenocorticotrophic hormone. Despite the early age of onset, no previous reports of pregnancy and GRA exist. Therefore, we set out to describe the maternal and fetal outcomes of pregnancy in women with GRA. Data regarding the blood pressure and pregnancy outcomes were collected in a retrospective chart review of prenatal and hospital records of 35 pregnancies in 16 women with genetically proven GRA. A total of 6% of pregnancies in women with GRA (GRA+) were complicated by preeclampsia. The published rates of preeclampsia in general obstetric populations vary from 2.5% to 10%. Despite the lack of an apparent increase in the rate of preeclampsia, GRA+ women with chronic hypertension had a high rate (39%) of pregnancy-aggravated hypertension. Starting with a higher baseline blood pressure, maternal blood pressure plotted over the time course of pregnancy followed a quadratic curve similar to that previously described in normal pregnancy. Mean gestational age at delivery was 39.1 weeks. Mean birth weight, excluding the 3 sets of twins, was 3219 g. However, infants of GRA+ mothers with pregnancy-aggravated hypertension tended to have lower birth weights than those that did not (3019 g versus 3385 g, respectively; P=0.08). The primary cesarean section rate was 32%, which is approximately double that seen in other general or hypertensive obstetric populations. In summary, GRA+ women did not seem to have an increased risk of preeclampsia. However, GRA+ women with chronic hypertension seem to be at an increased risk for an exacerbation of their hypertension during pregnancy.
Hypertension 2000 Feb
PMID:Glucocorticoid-remediable aldosteronism and pregnancy. 1067 15

Natural products like pumpkin-seed oil (PSO) may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACE-inhibitor), captopril (CPT) in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats (SHR) were investigated. SHR were treated orally with FEL at a dose of 0. 45 mg kg(-1) body wt. or CPT at a dose of 9 mg kg(-1) body wt. once daily for 4 weeks. PSO was administered at a dose of 40 mg kg(-1) body wt. alone or with FEL or CPT in the previous respective dose regimen for the same period to SHR. This study showed that hypertension induced increments the content of malondialdehyde (MDA) by 55% and 38% as well as the activity of glutathione peroxidase (GSH-Px) by 26% and 23% in heart and kidney, respectively, accompanied by reductions in the activity of myocardial superoxide dismutase (SOD) from 3.40+/-0.17 to 2.42+/-0.19 U mg protein(-1)and contents of glutathione (GSH) and protein thiols (PrSHs) in different tissues of SHR as compared to normotensive rats. Treatment of SHR with FEL or CPT monotherapy or combined with PSO produced improvement in the measured free radical scavengers in the heart and kidney. Our results also showed that pretreatment of SHR with PSO for 4 weeks then i.v. administration of FEL or CPT produced a significant beneficial hypotensive action. The results were explained in the light of the antioxidant properties of PSO. Therefore, it is concluded that concomitant administration of FEL or CPT with natural antioxidants can yield a beneficial therapeutic effect and retard the progression of hypertension.
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PMID:Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats. 1075 55

Cardiovascular disease is considered a probable risk factor of particulate matter (PM)-related mortality and morbidity. It was hypothesized that rats with hereditary systemic hypertension and underlying cardiac disease would be more susceptible than healthy normotensive rats to pulmonary injury from inhaled residual oil fly ash (ROFA) PM. Eight spontaneously hypertensive (SH) and eight normotensive Wistar-Kyoto (WKY) rats (12-13 weeks old) were implanted with radiotelemetry transmitters on Day -10 for measurement of electrocardiographic (ECG) waveforms. These and other nonimplanted rats were exposed to filtered air or ROFA (containing leachable toxic levels of metals) on Day 0 by nose-only inhalation (ROFA, 15 mg/m(3) x 6 h/day x 3 days). ECGs were monitored during both exposure and nonexposure periods. At 0 or 18 h post-ROFA exposure, rats were assessed for airway hyperreactivity, pulmonary and cardiac histological lesions, bronchoalveolar lavage fluid (BALF) markers of lung injury, oxidative stress, and cytokine gene expression. Comparisons were made in two areas: (1) underlying cardiopulmonary complications of control SH rats in comparison to control WKY rats; and (2) ROFA-induced cardiopulmonary injury/inflammation and oxidative burden. With respect to the first area, control air-exposed SH rats had higher lung and left ventricular weights when compared to age-matched WKY rats. SH rats had hyporeactive airways to acetylcholine challenge. Lung histology revealed the presence of activated macrophages, neutrophils, and hemorrhage in control SHrats. Consistently, levels of BALF protein, macrophages, neutrophils, and red blood cells were also higher in SH rats. Thiobarbituric acid-reactive material in the BALF of air-exposed SH rats was significantly higher than that of WKY rats. Lung inflammation and lesions were mirrored in the higher basal levels of pulmonary cytokine mRNA expression. Cardiomyopathy and monocytic cell infiltration were apparent in the left ventricle of SH rats, along with increased cytokine expression. ECG demonstrated a depressed ST segment area in SH rats. With regard to the second area of comparison (ROFA-exposed rats), pulmonary histology indicated a slightly exacerbated pulmonary lesions including inflammatory response to ROFA in SH rats compared to WKY rats and ROFA-induced increases in BALF protein and albumin were significantly higher in SH rats than in WKY rats. In addition, ROFA caused an increase in BALF red blood cells in SH rats, indicating increased hemorrhage in the alveolar parenchyma. The number of alveolar macrophages increased more dramatically in SH rats following ROFA exposure, whereas neutrophils increased similarly in both strains. Despite greater pulmonary injury in SH rats, ROFA-induced increases in BALF GSH, ascorbate, and uric acid were attenuated when compared to WKY rats. ROFA inhalation exposure was associated with similar increases in pulmonary mRNA expression of IL-6, cellular fibronectin, and glucose-6-phosphate dehydrogenase (relative to that of beta-actin) in both rat strains. The expression of MIP-2 was increased in WKY but attenuated in SH rats. Thus, SH rats have underlying cardiac and pulmonary complications. When exposed to ROFA, SH rats exhibited exacerbated pulmonary injury, an attenuated antioxidant response, and acute depression in ST segment area of ECG, which is consistent with a greater susceptibility to adverse health effects of fugitive combustion PM. This study shows that the SH rat is a potentially useful model of genetically determined susceptibility with pulmonary and cardiovascular complications.
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PMID:The spontaneously hypertensive rat as a model of human cardiovascular disease: evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. 1079 35

Several recent studies have shown that certain forms of genetic or acquired hypertension are associated with oxidative stress and that animals with those types of hypertension respond favorably to antioxidant therapy. We hypothesize that oxidative stress may cause hypertension via (among other mechanisms) enhanced oxidation and inactivation of nitric oxide (NO). To test this hypothesis, Sprague-Dawley rats were subjected to oxidative stress by glutathione (GSH) depletion by means of the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L in drinking water) for 2 weeks. The control group was given drug-free drinking water. In parallel experiments, subgroups of animals were provided vitamin E-fortified chow and vitamin C-supplemented drinking water. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of the NO metabolite nitrate plus nitrite, which suggests depressed NO availability. These characteristics were associated with a significant accumulation in various tissues of nitrotyrosine, which is the footprint of NO inactivation by reactive oxygen species. Administration of vitamin E plus vitamin C ameliorated hypertension, improved urinary nitrate-plus-nitrite excretion, and mitigated nitrotyrosine accumulation (despite GSH depletion) in the BSO-treated animals but had no effect in the control group. In conclusion, GSH depletion resulted in perturbation of the NO system and severe hypertension in normal animals. The effects of BSO were mitigated by concomitant antioxidant therapy despite GSH depletion, which supports the notion that oxidative stress was involved in the pathogenesis of hypertension in this model.
Hypertension 2000 Jul
PMID:Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. 1090 27

Ascorbic acid and glutathione (GSH) are important determinants of the intracellular redox state, and both are known to accelerate the decomposition of S-nitrosoglutathione (GSNO), an endogenous adduct of nitric oxide (NO). The implications of these observations for GSNO bioactivity are not yet clear. We investigated the effect of ascorbic acid and GSH on GSNO bioactivity by using a bioassay with isolated segments of guinea pig aorta suspended in organ chambers. Arterial segments demonstrated relaxation to GSNO (0.1 micromol/L) that was significantly enhanced by 300 micromol/L ascorbic acid (71+/-6% versus 53+/-6%, P<0.05) but not GSH. Both ascorbic acid and GSH significantly shortened the duration of arterial relaxation in response to 0.1 micromol/L GSNO (from >120 minutes to 22.5+/-3.5 and 36.3+/-4.3 minutes, respectively; P<0.05), consistent with accelerated decomposition of GSNO that was confirmed spectrophotometrically. The effect of ascorbic acid was abrogated by either DTPA or the copper(I)-specific agent bathocuproine but not deferoxamine, indicating a dependence on the availability of redox-active copper. Consistent with this notion, the action of ascorbic acid on GSNO bioactivity was also supported by copper-zinc superoxide dismutase, a physiologically relevant source of copper. In contrast, the effect of GSH on GSNO degradation and GSNO-mediated arterial relaxation was independent of transition metal ions, because DTPA had no effect. These data indicate that both ascorbic acid and GSH modulate GSNO bioactivity and suggest a distinction between the mechanism of GSNO degradation by ascorbic acid or GSH. Whereas both ascorbic acid and GSH accelerate the degradation of GSNO, only ascorbic acid is dependent on the presence of transition metal ions.
Hypertension 2000 Aug
PMID:Ascorbic acid and glutathione modulate the biological activity of S-nitrosoglutathione. 1094 92

Aldosterone, the major circulating mineralocorticoid, participates in blood volume and serum potassium homeostasis. Primary aldosteronism is a disorder characterised by hypertension and hypokalaemia due to autonomous aldosterone secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone:plasma renin activity ratio, have led to a suggestion that primary aldosteronism may be more common than previously appreciated among adults with hypertension. Glucocorticoid-remediable aldosteronism (GRA) was the first described familial form of hyperaldosteronism. The disorder is characterised by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be suppressed, on a sustained basis, by exogenous glucocorticoids such as dexamethasone in physiologic range doses. This autosomal dominant disorder has been shown to be caused by a hybrid gene mutation formed by a crossover of genetic material between the ACTH-responsive regulatory portion of the 11ss-hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperaldosteronism type I (FH-I), is characterised by autosomal dominant inheritance of autonomous aldosterone hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. The precise genetic cause of FH-II remains to be elucidated.
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PMID:Familial hyperaldosteronism. 1100 15

Gestational hypertension during the third trimester reflects an exaggerated maternal inflammatory response to pregnancy. We hypothesized that oxidative stress present even in normal pregnancy becomes uncompensated in hypertensive patients. A glucose-6-phosphate dehydrogenase (G6PD) activity sufficient to meet the increased reductive equivalent need of the cells is indispensable for defense against oxidative stress. The erythrocyte glutathione redox system was studied, where G6PD is the only NADPH source. The glutathione (GSH) redox status was measured both in vivo and after an in vitro oxidative challenge in pregnant women with gestational hypertension (n = 19) vs. normotensive pregnant subjects (n = 18) and controls (n = 20). An erythrocyte GSH depletion with an increase in the oxidized form (GSSG) resulted in an elevated ratio GSSG/GSH (0.305 +/- 0.057; mean +/- SD) in hypertensive pregnant women vs. normotensive pregnant or control subjects (0.154 +/- 0.025; 0.168 +/- 0.073; p <.001). In hypertensive pregnant patients, a "GSH stability" decrease after an in vitro oxidative challenge suggested a reduced GSH recycling capacity resulting from an insufficient NADPH supply. The erythrocyte GSSG/GSH ratio may serve as an early and sensitive parameter of the oxidative imbalance and a relevant target for future clinical trials to control the effects of antioxidant treatment in women at increased risk of the pre-eclampsia syndrome.
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PMID:Blood glutathione redox status in gestational hypertension. 1127 71

We assessed the hepatic antioxidant status of spontaneously (SHR) and desoxicorticosterone acetate (DOCA)-induced hypertensive rats and that of respective normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For this we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) content, glutathione-related enzyme (peroxidase, reductase and transferase) activities as well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant status and the cytotoxicity of acetaminophen, a radical- and hydrogen peroxide-mediated hepatotoxic compound, were also assessed in vitro in cultured hepatocytes isolated from hypertensive (SHR, DOCA) and normotensive control (WKY, SPRD) rats. Our results suggest that a difference exists in the hepatic antioxidant status between rat strains, with GSH levels being lower (-15%) and lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte cultures from WKY rats, both GSH content and catalase activity were lower (-30 and -70% respectively) compared to hepatocyte cultures from SPRD rats. This was associated with a 35% higher cytotoxicity of acetaminophen in cultured hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats. Hypertension in DOCA rats (mmHg: 221+/-9 vs. 138+/-5 in control SPRD rats) was associated with decreases (about 30%) in both glutathione peroxidase (GSH-Px) and catalase activities, ex vivo in livers and in vitro in hepatocyte cultures. Hypertension in SHR (mmHg: 189+/-7 vs. 130+/-5 in control WKY rats) was also associated with decreases (about 50%) in GSH-Px activity, ex vivo in livers and in vitro in hepatocyte cultures but catalase activity was not modified. The IC50 of acetaminophen was also lower in hepatocytes from hypertensive rats compared to respective controls, which could be related to the weakened antioxidant status in hepatocytes from hypertensive rats. Our data thus suggest that hepatocyte cultures are appropriated tools in which to assess hepatotoxicity and hepatoprotection in hypertension.
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PMID:Strain difference (WKY, SPRD) in the hepatic antioxidant status in rat and effect of hypertension (SHR, DOCA). Ex vivo and in vitro data. 1133 Aug 29

Development of hypertension, myocardial hypertrophy and the cardiac antioxidant status of male Dahl salt-sensitive (DSS) genetically hypertensive rats was evaluated and compared to that of normotensive Dahl salt-resistant (DSR) controls. In order to obtain exaggerated and more severe hypertension, half of the animals (10 per group) were Na loaded (8% NaCl diet) for 6 weeks. The myocardial antioxidant status was estimated in tissue homogenates on the basis of tissue glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The results showed that 6 weeks of hypertension resulted in left ventricle myocardial hypertrophy, documented by weight, morphometry and morphological changes. The compromised myocardial antioxidant status of the DSS rats was defined by significantly decreased GSH-Px and glutathione activity (13% and 41%, respectively) as compared to DSR rats. SOD in DSS myocardium was increased by 47% compared to that in DSR myocardium, an effect that is considered a compensatory mechanism to the oxidative stress. All of the above changes were exaggerated by NaCl loading. It was concluded that DSS rats, on either a normal or high NaCl diet, displayed decreased antioxidant capacity, which is most likely genetically determined. Before the Dahl rat can be considered as a suitable model for testing new cardiac antioxidants, a full characterization of the level of cardiac oxygen free radicals is required.
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PMID:Antioxidant status of the hypertrophic heart of Dahl hypertensive rat as a model for evaluation of antioxidants. 1141 64

Environmental factors such as diet, physical activity, drugs, pollution and life style play an important role in the progression and/or precipitation of diseases like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate use of antibiotics to combat infectious diseases is one of the commonest forms of misuse of drugs. Antibiotics seem to have a correlation with diabetes and pancreatic function. There are controversial reports about the effect of antibiotics on the pancreatic islets; some suggesting their harmless action, some depicting a beneficial role and others indicating deleterious effect. Moreover, use of antibiotics is mandatory during islet isolation and cultivation to reduce incidences of microbial contamination. It is likely that antibiotic treatment may adversely affect islet viability and its functioning leading to failure of islet transplantation. The present in vitro study was undertaken to examine the effect of commonly used antibiotics such as gentamycin, penicillin, streptomycin, tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its functioning and induction of oxidative stress if any. The viability and insulin production data showed that none of the antibiotics used in the present study affect the viability and the functioning of the islets at their pharmacological concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal increase in lipid peroxidation with tetracycline and slight increase in NO levels with streptomycin, none of these antibiotics affect the oxidative status of the cells. Antioxidant enzymes such as superoxide dismutase and catalase remain unaffected after this treatment. Our results reveal the innocuous nature of the antibiotics used at pharmacological concentrations, suggesting their safety whenever prescribed to combat infections and also during islet isolation procedures.
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PMID:Pancreatic islet-cell viability, functionality and oxidative status remain unaffected at pharmacological concentrations of commonly used antibiotics in vitro. 1156 80


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