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

To elucidate the role of oxygen free radicals and lipid peroxidation in the pathogenesis of early hypertension and atherosclerosis, we studied the native distribution of three primary arterial antioxidant enzymes (AEs). Specific immunohistochemical localization of superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) was examined in the arterial wall of New Zealand White rabbits: six sham-operated normotensive/normolipidemics (NT/NL), seven coarctation-induced hypertensive/normolipidemics (HT/NL), eight normotensive diet-induced hyperlipidemics (NT/HL), and six hypertensive/hyperlipidemics (HT/HL). All three AEs were confined primarily to the endothelium in NT/NL rabbit aortas. However, in HT and HL rabbits a greater proportion of the arterial wall, including the endothelium, inner media, and middle media, displayed immunolocalization of three AEs. Multiple linear-regression analysis revealed that more than 70% of the total variability in the depth of immunolocalization of arterial AEs could be explained by changes in blood pressure and/or total cholesterol. Also, levels of plasma and arterial cholesterol oxides were significantly different (p less than 0.05) in HT and HL rabbits compared with controls, with twofold increases in NT/HLs, threefold increases in HT/NLs, and fourfold increases in HT/HLs. We conclude that intense free-radical activity in the arterial wall of HT and HL animals is one possibility and that this occurs despite the presence of abundant AEs.
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PMID:Immunolocalization of native antioxidant scavenger enzymes in early hypertensive and atherosclerotic arteries. Role of oxygen free radicals. 155 32

Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.
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PMID:A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. 173 Dec 23

1. The activities of glutathione (GSH) transferases in male, spontaneously hypertensive rats (SHR) and stroke-prone rats (SHR-SP) were different from those of normotensive male Wistar Kyoto rats (WKY). 2. These alterations of the enzyme activities were partly due to the changes in the levels of subunits 2 and 4. 3. Subunit selective alterations were observed in pathophysiological conditions, namely spontaneous hypertension. 4. The sex-related difference of GSH transferases in these animals was also discussed.
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PMID:Subunit selective alteration of hepatic glutathione transferases in spontaneously hypertensive rats. 195 32

The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7-33 nmol) resulted in a dose-dependent increase in BP [delta mean BP: 17 +/- 1 mm Hg (n = 7) for 33-nmol dose] together with a marked increase in SNA [163 +/- 13 to 672 +/- 70 spikes/10 s (n = 7), p less than 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (delta mean BP: -9 +/- 2 mm Hg) accompanied by a corresponding decrease in SNA [192 +/- 15 to 54 +/- 22 spikes/10 s (n = 6), p less than 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.
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PMID:Brain glutathione and blood pressure control. 245 61

The role of brain glutathione metabolism in hypertensive animals was studied. In spontaneously hypertensive rats (SHR) from prehypertension to established hypertension, the content of oxidized glutathione (GSSG) and the ratio of GSSG to GSH in the hypothalamus were significantly (p less than 0.05) higher than those in age-matched normotensive Wistar Kyoto rats (WKY). Hypothalamic glutathione reductase (GR) activities in prehypertensive and established hypertensive SHR were significantly (p less than 0.05) lower than those in WKY. DOCA-salt hypertensive rats (DSR) also had a significantly (p less than 0.05) higher content of GSSG and GSSG/GSH ratio and a significantly (p less than 0.05) lower GR activity in the hypothalamus than the normotensive control. There were no significant differences in these values in the brain stem between hypertensive and normotensive rats. These results suggest that the increased GSSG/GSH ratio due to reduced activity of GR in the hypothalamus may have an important role in the development of hypertension in SHR and DSR.
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PMID:The role of hypothalamic glutathione in hypertensive animals. 324 1

The incipient timing of cerebral strokes in the stroke-prone spontaneously hypertensive rats (SHRSP) was biochemically determined by investigating the relationship between the glutathione peroxidase (GSH-Px) activity in erythrocytes and the extent of stroke lesions. When the blood pressure of SHRSPs was maintained at over 240 mmHg, the GSH-Px activity fell, and the body weight also decreased. In SHRSP whose GSH-Px activity in erythrocytes had dropped below 23 units/ml of blood, the incidence of cerebral strokes was 98% (n = 88/90). The hematocrit level did not change even after the GSH-Px activity had dropped to 23 units/ml of blood. The reduced GSH-Px activity in erythrocytes observed during continued hypertension was found to be due to a decrease in GSH-Px protein, and not to any inactivation of the enzyme, as evident from immunochemical titration. At the moment when the GSH-Px activity had dropped to 23 units/ml of blood, and the control diet was changed to one based on fish or a hydralazine treatment given, the activity recovered, and an increase in body weight and prolongation of the life-span were observed. It was deduced from these findings that tracing the GSH-Px activity in erythrocytes in SHRSP would serve as an indicator for predicting and prognosing stroke lesions.
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PMID:Prediction of stroke lesions in stroke-prone spontaneously hypertensive rats by glutathione peroxidase in erythrocytes. 754 98

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary cause of human hypertension in which aldosterone secretion is regulated by adrenocorticotropin (ACTH). A genetic mutation which causes GRA has recently been identified in our laboratory, a hybrid or chimeric gene fusing nucleotide sequences of the 11 beta-hydroxylase and aldosterone synthase genes. The finding that these chimeric gene duplications are sensitive and specific markers for GRA allows for a simple, direct genetic test for this disorder. In preliminary studies, we found a wide range of blood pressure levels (including normotension) in affected GRA subjects. Studies to data indicate that this is not related to environmental factors such as sodium intake. Another possibility is that chimeric gene expression is variable, with low blood pressure subjects having reduced gene expression. However, the data have not demonstrated differences in steroid levels in subjects with severe versus mild hypertension. In fact, it is likely that the wide range in blood pressure levels in affected subjects involves interaction of other systems which control blood pressure. Preliminary data in two kindreds suggest that blood pressure levels are reciprocally related to levels of urinary kallikrein excretion, supporting the notion that GRA is a hypertension-predisposing syndrome, with the resultant blood pressure the interaction of the gene mutation with other blood pressure regulatory systems. Although GRA is a mineralocorticoid excess state, as evidenced by profoundly suppressed levels of plasma renin activity, we have observed (contrary to the reported literature) that normokalemia is a typical finding. In one large normokalemic pedigree, preliminary findings indicate that these subjects have a normal capacity to excrete potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis. 779 15

Accelerated atherosclerotic vascular disease is the leading cause of mortality in patients with diabetes mellitus. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. Selective impairment of endothelium-dependent relaxation has been demonstrated in aortas of both nondiabetic animals exposed to elevated concentrations of glucose in vitro and insulin-dependent diabetic animals. The impaired NO release in experimentally induced diabetes may be prevented by a number of antioxidants. It has been hypothesized that oxygen-derived free radicals (OFR) generated during both glucose autoxidation and formation of advanced glycosylation end products may interfere with NO action and attenuate its vasodilatory activity. The oxidative injury may also be increased in diabetes mellitus because of a weakened defense due to reduced endogenous antioxidants (vitamin E, reduced glutathione [GSH]). A defective endothelium-dependent vascular relaxation has been found in animal models of hypertension and in hypertensive patients. An imbalance due to reduced production of NO or increased production of free radicals, mainly superoxide anion, may facilitate the development of an arterial functional spasm. Treatment with different antioxidants increases blood flow in the forearm and decreases blood pressure and viscosity in normal humans; vitamin E inhibits nonenzymatic glycosylation, oxidative stress, and red blood cell microviscosity in diabetic patients. Long-term randomized clinical trials of adequate size in secondary and primary prevention could support the free-radical hypothesis for diabetic diabetic vascular complications and the use of antioxidants to reduce the risk of coronary heart disease.
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PMID:Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress? 788 82

Several large family studies are reviewed to identify results suggesting single gene traits contributing to the occurrence of hypertension in humans. Segregation analysis in families has suggested major gene effects for several highly heritable traits associated with hypertension. These include recessively segregating high sodium-lithium countertransport (major gene H2 = 34%), additively segregating low urinary kallikrein excretion (major gene H2 = 51%), and recessively segregating hyperinsulinemia (major gene H2 = 33%). In some families, hypertension and metabolic abnormalities (dyslipidemia, hyperinsulinemia, and obesity) seem to be related to several candidate genes studied but not conclusively proven (LPL deficiency mutations, dense LDL subfractions, or NIDDM with hyperinsulinemia). More recently, DNA markers have identified genes promoting hypertension. Glucocorticoid-remediable aldosteronism (GRA) promotes a rare but unusual form of hypertension that is unresponsive to ordinary medications but very responsive to glucocorticoid medications. GRA has been found in hypertensive persons with a specific mutation of the 11 beta-hydroxylase gene on chromosome 8q21. Many persons with essential hypertension carry a common "susceptibility gene" at the angiotensinogen locus (chromosome 1q4) identified using linkage studies in siblings, association studies, and in studies of preeclampsia and hypertension in pregnant women. These first two well-established genetic loci promoting human hypertension represent two ends of a broad spectrum. The rare "determinant" gene for GRA by itself seems to produce severe hypertension and early strokes. The angiotensinogen (AGT) "susceptibility" gene is very common (30% of Utah Caucasians) and seems to predispose to hypertension but probably requires other genetic and environmental influences to be fully expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for single gene contributions to hypertension and lipid disturbances: definition, genetics, and clinical significance. 798 84

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant form of human hypertension. In GRA in which aldosterone secretion is positively and solely regulated by ACTH, glucocorticoid administration relieves this mineralocorticoid excess syndrome. Recent studies demonstrate that GRA is caused by a gene duplication fusing regulatory sequences of the steroid 11 beta-hydroxylase gene to the coding sequences of the aldosterone synthase gene. This gene mutation, which results in ectopic expression of aldosterone synthase activity in the zona fasciculata, provides the basis for a simple, direct genetic test for GRA from a small sample of peripheral blood.
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PMID:Glucocorticoid-remediable aldosteronism. 807 Apr 23


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