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)

Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and any relationship between the elevated MDA and lower vitamin E levels with hypertension in pregnant women. EDTA-Blood was collected from pregnant women at the time of delivery. Plasma vitamin E was determined by HPLC; MDA by the thiobarbituric acid-reactivity. Subjects with diastolic blood pressure (DBP) > or = 90 mm Hg were considered hypertensive (HT) and with < 90 mm Hg normotensive (NT). Data (Mean +/- SE) from 49 NT and 11 HT women show that HT has significantly lower vitamin E (22 +/- 1 vs 27 +/- 1 nmole/ml, p < 0.03) and elevated MDA levels (0.56 +/- 0.06 vs 0.43 +/- 0.02 nmole/ml, p < 0.03) compared to NT; the ages and gestational ages of women were similar. Among all women, there was a significant positive relationship between DBP and MDA levels (r = 0.27, p < 0.05), and a significant negative relationship between vitamin E levels and DBP (-0.36, p < 0.005), and a significant negative relationship between MDA and vitamin E levels (r = 0.27, p < 0.05). Thus, HT women's plasma has significantly lower E and higher MDA levels, and DBP significantly correlates with the extent of vitamin E deficiency and increased MDA levels. This study suggests a relationship between elevated lipid peroxidation and lower vitamin E levels and hypertension in pregnancy (preeclampsia).
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PMID:Relationship between elevated lipid peroxides, vitamin E deficiency and hypertension in preeclampsia. 858 11

The purpose of this study was to examine the effects of endothelin receptor inhibition on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). Structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were either untreated or treated for 3 months with bosentan, an inhibitor of endothelin receptors (100 mg/kg per day). We measured pressure, external diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated (EDTA) arterioles on the cerebrum. Bosentan reduced but did not normalize arteriolar mean pressure (103 +/- 3 and 81 +/- 5 mm Hg in untreated and treated SHRSP versus 51 +/- 4 mm Hg in WKY, P < .05; mean +/- SEM) and pulse pressure (40 +/- 2 and 33 +/- 2 mm Hg in untreated and treated SHRSP versus 25 +/- 3 mm Hg in WKY, P < .05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627 +/- 173 microm2), and CSA in treated SHRSP (1287 +/- 78 microm2) was similar to that in WKY (1299 +/- 65 microm2). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104 +/- 7 and 96 +/- 4 microm in untreated and treated SHRSP compared with 126 +/- 7 microm in WKY, P < .05). Stress-strain curves indicate that bosentan had no significant effect on distensibility of arterioles on the cerebrum in SHRSP. The results suggest that endothelin-1 may contribute to the development of hypertrophy, but not remodeling or changes in distensibility, of cerebral arterioles in SHRSP.
Hypertension 1996 Mar
PMID:Effects of endothelin receptor inhibition on cerebral arterioles in hypertensive rats. 861 42

Intestinal permeability was investigated by using 51Cr-EDTA as a probe molecule in 29 patients with immunoglobulin A nephropathy (IgA NP) and 20 healthy controls in 1990. Intestinal permeability was significantly higher in the IgA NP patients than in the controls (IgA NP, 3.86 +/- 0.29%; controls, 2.72 +/- 0.23%, p < 0.005). There was a significant relation between the manifestations of the disease (proteinuria and/or microhematuria) and the increased intestinal permeability (p < 0.05). By 1994, after an interval of 4 years, average intestinal permeability in the 21 patients available for study had not changed (3.80 +/- 0.36 vs. 4.57 +/- 0.63%) and was significantly higher than in the controls (p < 0.02). In patients with elevated serum IgA levels (serum IgA > 3.2 g/l; n = 15) there was a significant correlation between serum IgA levels and the degree of intestinal permeability (p < 0.02). During the 4-year period, the patients' kidney function deteriorated (n = 25; creatinine clearance in 1990, 92.4 +/- 6.1 ml/min; in 1994, 73.9 +/- 7.6 ml/min; p < 0.0002), the deterioration being greater in patients with increased intestinal permeability. There was no relation between the histologic grade of the biopsy specimen, hypertension and intestinal permeability. These data collected over a 4-year period suggest that in IgA NP increased intestinal permeability may play a role in the pathogenesis of the disease and adversely influence its progression.
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PMID:Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability. 895 61

Primary gout is characterized by increased plasma and decreased urinary concentrations of hypoxanthine, xanthine and uric acid. To examine whether lead could explain the disturbance of purine metabolism in gout, we determined hypoxanthine, xanthine and uric acid metabolism and 5-day cumulative urinary lead excretion rates after an EDTA (calcium disodium edetate) test in 27 patients with primary gout and reduced creatinine clearance (C(cr)) and in 50 patients with gout and normal C(cr). The results were compared to those obtained in 26 normal subjects matched for age. All gout patients evidenced a marked renal underexcretion of hypoxanthine, xanthine and uric acid relative to their increased plasma levels. Purine metabolism was remarkably similar in both gout groups except for a significantly lower uric acid excretion in patients with reduced C(cr). Blood lead levels and cumulative lead excretion rates were significantly higher in gout patients with renal failure as compared to patients with normal C(cr). Fourteen patients (52%) with renal insufficiency and 6 (12%) with normal C(cr) showed increased lead excretion rates (95% Cl for the difference, 29-51%, p < 0.001). Mobilizable lead was not significantly correlated with serum or urinary purine concentrations. Hypoxanthine, xanthine and uric acid underexcretion was similar in gout patients with increased or normal cumulative lead excretion rates. The prevalence of atheromatosis and arterial hypertension together was significantly higher in gout patients with renal failure than in patients with normal C(cr) (81 vs. 60%, 95% Cl for the difference, 11-31%, p < 0.005). These results indicate that lead is not a significant contributor to the renal underexcretion of purines in gout. An increased mobilizable lead is not by itself evidence that lead is the cause of the renal insufficiency in patients with primary gout. Atheromatous nephropathy and/or nephroangiosclerosis may explain impaired renal function in patients with primary gout.
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PMID:Purine metabolism in patients with gout: the role of lead. 906 56

1. KCl-induced contractions in aortic rings of spontaneously hypertensive rats (SHR) and two normotensive strains, Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats, were studied. 2. The contraction elicited by isotonic Na-free, KCl solution containing 2.5 mmol/L Ca and 1 mmol/L Mg was concentration-dependently inhibited by Na and K. Maximal inhibition was induced by 20 mmol/L NaCl in WKY and SHR (65 and 85%, respectively) and by 60 mmol/L NaCl in SD (50%). KCl (10-40 mmol/L) had no effect on SD but produced almost full relaxation in WKY and about 50% relaxation in SHR. 3. Isotonic Ca-free, Na-free high Mg (2 mmol/L), K-solution caused strong phasic contractions in WKY and SHR, but weak responses in SD. 4. Aortic rings of SD, WKY and SHR developed strong, sustained and reproducible contractions in isotonic Ca-free, Na-free, K-solution containing EDTA, which were fully relaxed by 1.2, 1.6 and 8 mmol/L Na, respectively. 5. We suggest that the primary mechanism of KCl-contraction is potential-independent competition between monovalent and divalent cations for binding sites on both surfaces of the plasma membrane (e.g. K with Mg and Na with Ca) and that differences in aortic contractility in SHR, WKY and SD merely reflect strain differences in the composition of the ionic matrix, independent of hypertension.
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PMID:Regulation of vascular contraction by ionic matrix surfaces of the smooth muscle cell: changes in SHR? 907 72

Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content.
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PMID:Renal effects of environmental and occupational lead exposure. 930 Sep 27

According to present knowledge, altered arterial reactivity associated with hypertension, atherosclerosis and hypercholesterolemia is related to impaired release of endothelial derived relaxing factor (EDRF). Impaired relaxation followed by enhanced vasoconstriction leads to a well known clinical entities such as unstable angina, acut myocardial infarction. Impairment of EDRF may also account for smooth muscle cell proliferation and migration. Aim of present study was to examine the endothelial dependent response during in vitro conditions in human femoral arteries taken from bypass operation and leg amputation. Examining the contractility, the effect was modulated with nifedipin, EDTA and pertussis toxin, respectively. Endothelium dependent relaxation to acethylcholin and histamine were markedly diminished, while those to calcium ionophore were maintained throughout the study. These results suggest that at least two or more receptor-coupled system may be involved in generation of EDRF. However, direct relaxation of femoral artery to nitrovasodilatators (nitroglycerine) were comparable between control and atherosclerotic artery. Another striking change in atherosclerotic artery was the increased sensitivity to the vasoconstrictions. To eluciadate to exact biochemical mechanism underlying the endothelial dysfunction may help to develop a new vasodilatator drug.
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PMID:[In vitro study of endothelium-dependent relaxation and contraction of human atherosclerotic femoral artery]. 934 May 78

Angiotensin converting enzyme (ACE) inhibitors augment circulating levels of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] in man and animals. Increased concentrations of the peptide may contribute to the antihypertensive effects associated with ACE inhibitors. The rise in Ang-(1-7) following ACE inhibition may result from increased production of the peptide or inhibition of the metabolism of Ang-(1-7)-similar to that observed for bradykinin. To address the latter possibility, we determined whether Ang-(1-7) is a substrate for ACE in vitro. In a pulmonary membrane preparation, the ACE inhibitor lisinopril attenuated the metabolism of low concentrations of 125I-Ang-(1-7). The primary product of 125I-Ang-(1-7) metabolism was identified as Ang-(1-5). Using affinity-purified ACE from canine lung, HPLC separation and amino acid analysis revealed that ACE functioned as a dipeptidyl carboxypeptidase cleaving Ang-(1-7) to the pentapeptide Ang-(1-5). The ACE inhibitors lisinopril and enalaprilat (1 micromol/L), as well as the chelating agents EDTA, o-phenanthroline, and DTT (0.1-1 mmol/L) abolished the generation of Ang-(1-5) and did not yield other metabolic products. Ang-(1-5) was not further hydrolyzed by ACE. Kinetic analysis of the hydrolysis of Ang-(1-7) by ACE revealed a substrate affinity of 0.81 micromol/L and maximal velocity of 0.65 micromols min(-1) mg(-1). The calculated turnover constant for the peptide was 1.8 sec(-1) with a catalytic efficiency (Kcat/Km) of 2200 sec(-1) mmol/L(-1). These findings suggest that increased levels of Ang-(1-7) following ACE inhibition may be due, in part, to decreased metabolism of the peptide.
Hypertension 1998 Jan
PMID:Metabolism of angiotensin-(1-7) by angiotensin-converting enzyme. 945 29

The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.
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PMID:A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years. 945 89

Activated polymorphonuclear leukocytes release heparin-binding protein (HBP; also known as CAP37 or azurocidin) from azurophilic granules. HBP is a strong chemoattractant for monocytes that also prolongs monocyte survival and potentiates endotoxin (lipopolysaccharide [LPS])-induced production of tumor necrosis factor alpha (TNF-alpha). We investigated the binding of fluorescein isothiocyanate-conjugated HBP to human monocytes in the presence of EDTA and the polysaccharide fucoidan. EDTA, which chelates divalent cations, has been widely used to study the role of divalent cations in receptor-ligand interactions or enzyme activity. Fucoidan has been used to inhibit the binding of various ligands to scavenger receptors or selectins. Scavenger receptors are multiligand receptors that mediate endocytosis of proteases, protease-inhibitor complexes, lipoproteins, and LPS-lipid A. Fucoidan also interferes with leukocyte rolling by binding to L-selectins (expressed on leukocytes) and P-selectins (expressed on platelets and endothelium). We demonstrate that the binding of the neutrophil-derived protein HBP to monocytes is inhibited in the presence of EDTA and fucoidan. In addition, fucoidan and EDTA abrogate the enhancing effect of HBP on LPS-induced TNF-alpha production. These data provide supporting evidence that HBP binds to a receptor expressed on monocytes. This receptor is dependent on divalent cations and is possibly related to the scavenger receptor. Furthermore, we demonstrate that fucoidan, by itself, stimulates TNF-alpha release from isolated monocytes in a CD14-independent fashion. This is an important finding for the interpretation of results from studies that use fucoidan to "block" either scavenger receptors or L- or P-selectins.
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PMID:Modulation of lipopolysaccharide-induced monocyte activation by heparin-binding protein and fucoidan. 982 63


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