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)

To evaluate the effect of hypertension on glycosaminoglycan (GAG) synthesis, cultured vascular smooth muscle cells (CVSMCs) from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were exposed to centrifugal forces and catecholamines. GAG synthesis of CVSMCs was measured by the incorporation of [3H]glucosamine into GAGs which were secreted into the culture medium for 24 h. Basal level of GAG synthesis was much higher in SHR than in WKY, when expressed in terms of DNA contents. When exposed to centrifugal force, CVSMCs from rats of both strains synthesized more GAGs. GAG synthesis was enhanced by both noradrenaline (NA) and adrenaline (Ad) in WKY. The enhanced GAG synthesis in WKY by NA or Ad was prevented by pretreatment with propranolol, but not prazosin. In SHR, NA and Ad did not enhance GAG synthesis at this concentration of catecholamines. However, the effects of propranolol or prazosin on GAG synthesis in SHR, when incubated with either NA or Ad, were compatible with the phenomena observed in WKY. Adding dibutyryl cyclic AMP to the culture medium enhanced GAG synthesis in rats of both strains. These data suggest that not only the mechanical stress of high intra-arterial pressure but also beta receptor stimulation, via increasing cyclic AMP, enhance GAG synthesis of vascular smooth muscle cells in hypertension.
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PMID:Effect of centrifugal force and catecholamines on glycosaminoglycans synthesis of vascular smooth muscle cells in culture. 224 93

The biochemical changes in the articular cartilage of the femoral condyles and the patella were studied during the earliest stage of patello-femoral arthrosis, with particular reference to chondromalacia of the patella in the "lateral hypertension syndrome", with the object of comparing them with the results obtained by Boni et al. (1977) in the initial phases of experimental arthrosis induced in rabbits by means of vitamin A. The biochemical determinations were done on samples of cartilage removed at operation from the medial and lateral femoral condyles and the medial and lateral patellar articular facets in ten patients. The biopsy samples were fixed in 80% alcohol and dried in the oven at 50 degrees C for twenty-four hours. The hexosamine and hydroxyproline content was then determined. This investigation demonstrated significant biochemical changes in this syndrome in the four areas examined. The data obtained indicate that only the mucopolysaccharide component of the joint cartilage is involved at this stage. The most interesting finding was marked diminution in the galactosamine/glucosamine ratio, which was markedly diminished - the opposite of what occurs in established arthrosis. These data appear to be identical with those found in the early phases of vitamin A induced arthrosis in experimental rabbits. The diminution of hexosamine content and the diminished galactosamine/glucosamine ratio were more marked in the femoral condyles, which appeared to have few lesions macroscopically. These changes were also present in both articular facets of patella, but were less marked, probably because the degeneration was more advanced in those areas, thus more closely resembling frank arthrosis.
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PMID:Biochemical changes in the articular cartilage of the patella and femoral condyles in the lateral hyperpatellar syndrome. 734 33

Calcium antagonists are the gold standard in the therapy of coronary heart disease and hypertension. The prototype of these drugs is nifedipine which, as well as its therapeutic effects on the cells of the cardiovascular system, also has unpleasant side effects on other organ systems. One side effect can be a missive hyperplasia of the gingiva, the reason for which are unclear. In vitro experiments were designed to elucidate the influence of nifedipine on the growth of human gingival fibroblasts in short and long term (72 hours, 6 weeks) cell culture. The following cellular parameters were determined quantitatively: cell proliferation (cell count, [3H]thymidine incorporation), protein synthesis ([3H]glucosamine incorporation) and viability (release of lactate dehydrogenase). A significant increase in cell proliferation (up to 1 microgram/ml nifedipine) was observed in the short-term experiments (72 hours, 0.001-10 micrograms/ml nifedipine), no other parameters were altered or were even depressed at higher concentrations. A significant increase in the cell proliferation and a decrease in the proteoglycan synthesis was found in the long term experiments (6 weeks, 1 microgram/ml nifedipine). Our results indicate that nifedipine has a direct effect on the cell proliferation of the gingival fibroblast in cell culture. The effect of nifedipine on the gingival fibroblasts are therefore similar to those observed earlier by the widely used immunosuppressant drug cyclosporin A on human gingival fibroblast in culture.
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PMID:Influence of nifedipine on the metabolism of gingival fibroblasts. 807 4

The mechanism of edema, proteinuria, hypertension (EPH)-gestosis-associated premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs) in the umbilical cord arteries is not known. It may result from altered biosynthesis, a different degradation rate or a combination of both phenomena. In order to solve this problem, it was decided to evaluate the biosynthesis and degradation of newly synthesized GAGs in the umbilical cord arteries of control newborns and those delivered by mothers with EPH-gestosis. Incorporation of radioactive precursors ([14C]glucosamine and [35S]sulphate) into GAGs and degradation of newly synthesized GAGs using the pulse-chase experiment were evaluated. We found that the investigated tissue slices incorporated distinctly less [14C]glucosamine into hyaluronic acid in comparison to controls. In contrast to that, the biosynthesis of sulphated GAGs did not change significantly. However, the degradation of newly synthesized sulphated GAGs was distinctly slower than in control tissues. It may be concluded that an EPH-gestosis associated decrease in hyaluronic acid content in the umbilical cord artery is a result of decreased biosynthesis of this substance, whereas an increase in sulphated GAGs-content is rather a result of slower degradation of newly synthesized GAGs.
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PMID:Glycosaminoglycan-biosynthesis in the wall of the umbilical cord artery and its alteration in EPH-gestosis. 907 17

Extracellular matrix (ECM) modifications in the vascular wall contribute to the narrowing of arteries in hypertension. Because direct evidence for the role of proteoglycans (PGs) in the pathological process of resistance-sized arteries has not already been demonstrated, we examined the effect of growth factors on secreted and membrane-bound PG synthesis by cultured mesenteric vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar rats. After 48 hours of stimulation with angiotensin II (Ang II), platelet-derived growth factor (PDGF-BB), and 10% fetal calf serum (FCS) or 0.1% FCS as control, PG synthesis (in dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic label method with both [(3)H]-glucosamine and [(35)S]-sodium sulfate, which are incorporated into all complex carbohydrates or only into sulfated disaccharides, respectively. VSMC from SHR displayed a significantly lower level of synthesis of M-ECM [(3)H]-PGs than those of Wistar rats in all the experimental groups, including the control group (0. 1% FCS), but no differences in M-ECM [(35)S] uptake were found in any case. In the P-ECM, Ang II was the only factor that produced a lesser effect on [(3)H]-glucosamine and a greater effect on [(35)S]-sodium sulfate uptakes in VSMC from SHR than from Wistar rats. The most prominent change seen in VSMC from SHR was an increased sulfation, assessed by [(35)S]/[(3)H] ratio, in nonstimulated cells and in response to 10% FCS and Ang II but not to PDGF-BB compared with VSMC from Wistar rats. These data indicate the existence of changes in PG modulation in the resistance vessels of SHR, which suggests that PGs may contribute to the development of structural and functional modifications in hypertensive states.
Hypertension 1999 Oct
PMID:Proteoglycan production by vascular smooth muscle cells from resistance arteries of hypertensive rats. 1052 80

Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin-resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions that are directly correlated to hypertension. We examined whether hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression and whether obesity and insulin resistance are associated with abnormal AGT regulation. In addition, because the hexosamine biosynthetic pathway is considered to function as a biochemical sensor of intracellular nutrient availability, we hypothesized that activation of this pathway would acutely mediate in vivo the induction of AGT gene expression in fat and liver. We studied chronically catheterized lean (approximately 300 g) and obese (approximately 450 g) Sprague-Dawley rats in four clamp studies (n = 3/group), creating physiological hyperinsulinemia (approximately 60 microU/ml, by an insulin clamp), hyperglycemia (approximately 18 mM, by a pancreatic clamp using somatostatin to prevent endogenous insulin secretion), or euglycemia with glucosamine infusion (GlcN; 30 micromol. kg(-1). min(-1)) and equivalent saline infusions (as a control). Although insulin infusion suppressed AGT gene expression in fat and liver of lean rats, the obese rats demonstrated resistance to this effect of insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene expression in fat and liver by approximately threefold in both lean and obese rats (P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results support the hypothesis that physiological nutrient "pulses" may acutely induce AGT gene expression in both adipose tissue and liver through the activation of the hexosamine biosynthetic pathway. Resistance to the suppressive effect of insulin on AGT expression in obese rats may potentiate the effect of nutrients on AGT gene expression. We propose that increased AGT gene expression and possibly its production may provide another link between obesity/insulin resistance and hypertension.
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PMID:Hyperglycemia modulates angiotensinogen gene expression. 1150 94

Remodeling of large and small arteries contributes to the development and complications of hypertension. Artery structural changes in chronic sustained hypertension include vascular smooth muscle cells (VSMC) proliferation and extracellular matrix (ECM) modifications. Extracellular constituents such as proteoglycans (PGs), may modulate vascular stiffness and VSMC growth and differentiation. We examined the effect of growth factors on secreted and membrane-bound PGs synthesis by cultured aortic smooth muscle cells (SMC) from 12- to 14- week-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats. After stimulation with platelet-derived growth factor (PDGF-BB), 10% fetal calf serum (FCS) or 0.1% FCS as control, PGs synthesis (dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic label method using both [3H]-glucosamine and [35S]-sodium sulfate which are incorporated into all complex carbohydrates or only into sulfated dysaccharides, respectively. Data are presented as percent of the control (0.1% FCS). SHR VSMC displayed a significantly greater synthesis of M-ECM [3H]-PGs than Wistar rat cells, with both treatments, but no differences in M-ECM [35S] uptake were found in any case. In the P-ECM, both PDGF-BB and 10% FCS produced a greater effect on [3H]-PGs and sulfated PGs synthesis in VSMC from SHR. An important change seen in SHR cells was a significant decreased sulfation, assessed by [35S]/[3H] ratio, in basal and stimulation conditions. Present results indicate the existence of changes in PGS synthesis and modulation in VSMC from a conduit-artery of SHR and support the pathophysiological role proposed for matrix proteoglycans in the vascular wall changes associated to hypertension and related vascular diseases as atherosclerosis.
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PMID:Proteoglycans production by aortic vascular smooth muscle cells from hypertensive rats. 1451 Feb 37

Many adverse effects of glucose were attributed to its increased routing through the hexosamine pathway (HBP). There is evidence for an autocrine role of the insulin signaling in beta-cell function. We tested the hypothesis that activation of the HBP induces defects in insulin biosynthesis by affecting the insulin-mediated protein translation signaling. Exposure of human pancreatic islets and RIN beta-cells to glucosamine resulted in reduction in glucose- and insulin-stimulated insulin biosynthesis, which in RIN beta-cells was associated with impairment in insulin-stimulated insulin receptor substrate-1 (IRS-1) phosphorylation at Tyr(608) and Tyr(628), which are essential for engaging phosphatidylinositol 3-kinase (PI 3-kinase). These changes were accompanied by impaired activation of PI 3-kinase, and activation of Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway. RIN beta-cells exposed to high glucose exhibited increased c-Jun N-terminal kinase (JNK) and ERK1/2 activity, which was associated with increased IRS-1 phosphorylation at serine (Ser)(307) and Ser(612), respectively, that inhibits coupling of IRS-1 to the insulin receptor and is upstream of the inhibition of IRS-1 tyrosine phosphorylation. Azaserine reverted the stimulatory effects of high glucose on JNK and ERK1/2 activity and IRS-1 phosphorylation at Ser(307) and Ser(612). Glucosamine mimicked the stimulatory effects of high glucose on JNK and ERK1/2 activity and IRS-1 phosphorylation at Ser(307) and Ser(612). Inhibition of JNK and MAPK kinase-1 activity reverted the negative effects of glucosamine on insulin-mediated protein synthesis. These results suggest that activation of the HBP accounts, in part, for glucose-induced phosphorylation at Ser(307) and Ser(612) of IRS-1 mediated by JNK and ERK1/2, respectively. These changes result in impaired coupling of IRS-1 and PI 3-kinase, and activation of the Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway.
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PMID:Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells. 1500 44

Because adverse effects of glucose were attributed to its increased routing through the hexosamine pathway (HBP), we inquired whether HBP activation affects pancreatic beta-cell survival. Exposure of human islets to high glucose resulted in increased apoptosis of beta-cells upon serum deprivation that was reversed by azaserine. Also, glucosamine, a direct precursor of the downstream product of the HBP, increased human beta-cells apoptosis upon serum deprivation, which was reversed by benzyl-2-acetamido-2-deoxy-alpha-d-galactopyranoside (BADGP), an inhibitor of protein O-glycosylation. These results were reproduced in RIN rat beta-cells. Glucosamine treatment resulted in inhibition of tyrosine-phosphorylation of the insulin receptor (IR), IRS-1, and IRS-2, which was associated with increased O-glycosylation. These changes caused impaired activation of the PI 3-kinase/Akt survival signaling that resulted in reduced GSK-3 and FOXO1a inactivation. BADGP reversed the glucosamine-induced reduction in insulin-stimulated phosphorylation of IR, IRS-1, IRS-2, Akt, GSK-3, and FOXO1a. Impaired FOXO1a inactivation sustained expression of the pro-apoptotic protein Bim, without affecting Bad, Bcl-XL, or Bcl-2 expression. These results indicate that hyperglycemia may increase susceptibility to apoptosis of human and rat beta-cell through activation of the HBP. Increased routing of glucose through this metabolic pathway results in impaired activation of the IR/IRSs/PI3-kinase/Akt survival pathway by induction of O-glycosylation of signaling molecules.
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PMID:Increased O-glycosylation of insulin signaling proteins results in their impaired activation and enhanced susceptibility to apoptosis in pancreatic beta-cells. 1505 79

Previous studies have suggested that patients with chronic medical conditions use complementary and alternative medicine (CAM) at a higher rate than the general population. Despite recent interest in CAM for cardiovascular disease, few data are available regarding patterns of use in patients with cardiovascular disease in the United States. This study used the 2002 National Health Interview Survey and analyzed data on CAM use in 10,572 respondents with cardiovascular disease. Among those with cardiovascular disease, 36% had used CAM (excluding prayer) in the previous 12 months. The most commonly used therapies were herbal products (18%) and mind-body therapies (17%). Among herbs, echinacea, garlic, ginseng, ginkgo biloba, and glucosamine with or without chondroitin were most commonly used. Among mind-body therapies, deep-breathing exercises and meditation were most commonly used. Overall, CAM was used most frequently for musculoskeletal complaints (24% of respondents who used mind-body therapies, 22% who used herbs, 45% who used any CAM). Mind-body therapies were also used for anxiety or depression (23%) and stress or emotional health and wellness (16%). Herbs were commonly used for head and chest colds (22%). Fewer respondents (10%) used CAM specifically for their cardiovascular conditions (5% for hypertension, 2% for coronary disease, 3% for vascular insufficiency, < 1% for heart failure or stroke). Most, however, who used CAM for their cardiovascular condition perceived the therapies to be helpful (80% for herbs, 94% for mind-body therapies). CAM use was more common in younger respondents, women, Asians, and those with more education and greater incomes. In conclusion, CAM use, particularly herbs and mind-body therapies, is common in the United States in patients with cardiovascular disease and mirrors use in the general population. CAM use specifically to treat cardiovascular conditions, however, is less common.
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PMID:Use of complementary therapies in patients with cardiovascular disease. 1692 60


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