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

The aim of this study was to ascertain whether the presence of hypertension conveys a more severe degree of insulin resistance in type 2 diabetes mellitus and, if so, which biochemical pathways are involved. We quantitated the rates of total glucose disposal, glycogen synthesis (GS), glycolysis, glucose oxidation, endogenous glucose production, and LOX in the basal state and during a 4-h euglycemic ( approximately 5 mM) hyperinsulinemic ( approximately 300 pM) clamp carried out in combination with a dual-tracer infusion ([(3)H]-3- and [(14)C]-U-D-glucose) and indirect calorimetry in 42 nonobese noninsulin-treated type 2 diabetic subjects (22 hypertensive and 20 normotensive) and 23 nonobese nondiabetic subjects (9 without and 14 with essential hypertension). Compared with normotensive controls, both groups of diabetic subjects were markedly insulin resistant. In the basal state, all glucose fluxes were similar in diabetic subjects with or without hypertension. During insulin infusion, total glucose disposal was significantly reduced in hypertensive diabetic subjects, compared with their normotensive counterparts (18.7 +/- 1.0 vs. 28.6 +/- 3.0 micromol/min.kg lean body mass; P < 0.01). This difference was almost entirely explained by a marked reduction in GS (4.5 +/- 2.0 vs. 12.5 +/- 3.3 micromol/min.kg lean body mass; P < 0.01). Endogenous glucose production was not different in the two diabetic groups during insulin infusion and was significantly higher than in normotensive controls. Lipid oxidation was less suppressed by hyperinsulinemia in hypertensive than in normotensive diabetic subjects (1.46 +/- 0.1 vs. 0.91 +/- 0.1 micromol/min.kg lean body mass; P < 0.01). Glucose fluxes were not significantly different in nondiabetic subjects with essential hypertension and in normotensive diabetic individuals. These results indicate that hypertension markedly aggravates insulin resistance featuring type 2 diabetes mellitus. The molecular defects underlying this phenomenon involve primarily GS.
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PMID:Intracellular partition of plasma glucose disposal in hypertensive and normotensive subjects with type 2 diabetes mellitus. 1134 9

The quantitative autoradiographic 2-[(14)C]-deoxy-D-glucose methods were used to assess the local cerebral glucose utilization (LCGU) in 46 brain structures in rats suffering from heatstroke. Heatstroke was induced by exposing the animals to an ambient temperature of 42 degrees C. The time at which the local cerebral blood flow (CBF) and mean arterial pressure (MAP) decreased from their peak levels was taken as the onset of heatstroke. Control rats were exposed to a temperature of 24 degrees C. The values of local CBF, MAP and means of total LCGU after heatstroke onset were all significantly lower than those in control rats. However, the values of colonic temperature were greater. Thus, it appears that the decreased cerebral metabolism and perfusion can be due to secondary effect of hypertension after heatstroke onset.
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PMID:Local cerebral glucose utilization decreases after heatstroke onset in rats. 1147 24

This study investigates the effects of candesartan, an angiotensin II type 1 receptor blockade, on carotid arterial intimal thickening and glucose tolerance in balloon-injured male Wistar fatty rats and their littermates (Wistar lean rats). Candesartan was orally administered to 12-week-old rats for 21 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 7, and the artery was removed on day 14 for histological analysis. Compared with the area ratios of the neointima/media in fatty rats without treatment, the ratios in fatty rats treated with candesartan at 1 mg. kg(-1). d(-1) and lean rats without treatment were significantly decreased to 65%; on the other hand, the ratios of fatty rats treated with candesartan at 10 mg. kg(-1). d(-1) and lean rats treated with 1 mg. kg(-1). d(-1) were reduced to 35%, and those of lean rats treated with 10 mg. kg(-1). d(-1) were reduced to 28%. The administration of candesartan also decreased the level of plasma glucose time- and dose-dependently in fatty rats. In an intragastric glucose load, the levels of both glucose and insulin at 30 and 60 minutes were significantly decreased when fatty rats were treated with candesartan at 10 mg. kg(-1). d(-1). In cultured vascular smooth muscle cells from fatty rats, insulin-stimulated Akt (New England Biolabs) phosphorylation and 2-deoxy-D-glucose uptake were inhibited to 59% and 68%, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10(-7) mol/L candesartan. We conclude that candesartan could be effective for the suppression of vascular smooth muscle cell growth dose-dependently in Wistar fatty and lean rats. Furthermore, the agent could improve insulin resistance in Wistar fatty rats.
Hypertension 2001 Dec 01
PMID:Candesartan inhibits carotid intimal thickening and ameliorates insulin resistance in balloon-injured diabetic rats. 1175 99

The aim of the present study was to investigate whether a dietary supplementation of alpha-lipoic acid could prevent blood pressure elevation, insulin resistance, and the increase in aorta superoxide anion production in a new experimental model of hypertension associated with insulin resistance. Sprague-Dawley rats were given 10% D-glucose in their drinking water combined either with a normal chow diet or with an alpha-lipoic acid-supplemented diet and were compared with control rats during 3 weeks. Oxidative stress was evaluated by measuring the aortic superoxide anion production using the lucigenin chemiluminescence method. Increases in blood pressure, insulin resistance, and aorta superoxide production observed in glucose-fed rats were prevented by the supplementation of the diet with lipoic acid. Positive correlations were found between aortic superoxide production and blood pressure, between insulin resistance and blood pressure, or between superoxide production and insulin resistance. Moreover, a decrease in the activity of plasma glutathione peroxidase observed in the glucose-fed rats was prevented by lipoic acid treatment. These findings demonstrate that high-glucose feeding rapidly induced hypertension and insulin resistance in association with the induction of a vascular oxidative stress. The antihypertensive action and the prevention of insulin resistance by lipoic acid appears to be associated to its antioxidative properties because it prevented the increase in oxidative stress, as reflected by the normalization of superoxide anion production in aorta and the prevention of the fall in the activity of glutathione peroxidase in the glucose-fed rats.
Hypertension 2002 Feb
PMID:Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. 1184 2

The renin-angiotensin-aldosterone-system appears to be involved in the development of cardiac fibrosis in rodents, characterized by nonepithelial cell proliferation and changes in the extracellular matrix. The aim of our study was to investigate the effect of high aldosterone concentrations on the proliferation of human cardiac interstitial cells in vitro. In addition, the effect of D-glucose as another risk factor for fibrosis, eg, in the diabetic heart, was investigated. Human cardiac myofibroblast cultures were established, and growth rates were measured by WST-1 assay in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). Cells in culture showed a significant increase in number between 24 to 72 hours of cultivation under basal conditions (DMEM, 10% fetal calf serum). Aldosterone at high concentrations (10(-8) and 10(-7) mol/L) significantly (P<0.01) increased the proliferation of cultured cardiac myofibroblasts. Comparable effects were observed after incubation of the cells with high D-glucose concentrations (15 and 25 mmol/L, P<0.01). No additive growth stimulation was evident when the cells were incubated in medium containing both aldosterone and D -glucose. These results suggest a role for aldosterone and glucose in mediating the cardiac fibrosis through stimulation of myofibroblast growth in patients with dysregulated renin-angiotensin-aldosterone-system (especially hyperaldosteronism) and impaired glucose homeostasis.
Hypertension 2002 Mar 01
PMID:Aldosterone and D-glucose stimulate the proliferation of human cardiac myofibroblasts in vitro. 1189 58

The present study describes characteristic features of two clonal subpopulations of opossum kidney (OK) cells (OK(LC) and OK(HC)) that are functionally different but morphologically identical. The most impressive differences between OK(HC) and OK(LC) cells are the overexpression of Na+-K+-ATPase and type 3 Na+/H+ exchanger by the former, accompanied by an increased Na+-K+-ATPase activity (57.6 +/- 5.6 vs. 30.0 +/- 0.1 nmol P(i). mg protein(-1). min(-1)); the increased ability to translocate Na+ from the apical to the basolateral surface; and the increased Na+-dependent pH(i) recovery (0.254 +/- 0.016 vs. 0.094 +/- 0.011 pH units/s). Vmax values (in pH units/s) for Na+-dependent pHi recovery in OK(HC) cells (0.00521 +/- 0.0004) were twice (P < 0.05) those in OK(LC) (0.00202 +/- 0.0001), with similar Km values (in mM) for Na+ (OK(LC), 21.0 +/- 5.5; OK(HC), 14.0 +/- 5.6). In addition, we measured the activities of transporters (organic ions, alpha-methyl-D-glucoside, L-type amino acids, and Na+ and enzymes (adenylyl cyclase, aromatic L-amino acid decarboxylase, and catechol-O-methyltransferase). The cells were also characterized morphologically by optical and scanning electron microscopy and karyotyped. It is suggested that OK(LC) and OK(HC) cells constitute an interesting cell model for the study of renal epithelial physiology and pathophysiology, namely, hypertension.
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PMID:Expression and function of sodium transporters in two opossum kidney cell clonal sublines. 1206 May 89

Improvement of insulin resistance by ACE inhibitors has been suggested; however, this mechanism has not been proved. We postulated that activation of the bradykinin-nitric oxide (NO) system by an ACE inhibitor enhances glucose uptake in peripheral tissues by means of an increase in translocation of glucose transporter 4 (GLUT4), resulting in improvement of insulin resistance. Administration of an ACE inhibitor, temocapril, significantly decreased plasma glucose and insulin concentrations in type 2 diabetic mouse KK-Ay. Mice treated with temocapril showed a smaller plasma glucose increase after glucose load. We demonstrated that temocapril treatment significantly enhanced 2-[3H]-deoxy-D-glucose (2-DG) uptake in skeletal muscle but not in white adipose tissue. Administration of a bradykinin B2 receptor antagonist, Hoe140, or an NO synthase inhibitor, L-NAME, attenuated the enhanced glucose uptake by temocapril. Moreover, we observed that translocation of GLUT4 to the plasma membrane was significantly enhanced by temocapril treatment without influencing insulin receptor substrate-1 phosphorylation. In L6 skeletal muscle cells, 2-DG uptake was increased by temocaprilat, and Hoe140 inhibited this effect of temocaprilat but not that of insulin. These results suggest that temocapril would improve insulin resistance and glucose intolerance through increasing glucose uptake, especially in skeletal muscle at least in part through enhancement of the bradykinin-NO system and consequently GLUT4 translocation.
Hypertension 2002 Sep
PMID:ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and NO. 1221 75

Patients with chronic kidney disease often require surgical interventions for vascular access and for medical problems related to comorbid conditions. Perioperative morbidity and mortality rates are increased in these patients. Preoperative attention to common medical problems that occur in patients with impaired renal function can lower some surgical risks. Hyperkalemia can be temporarily improved by the intravenous administration of an insulin-dextrose combination or bicarbonate, and polystyrene binding resins or dialysis can remove excess stores of potassium. Increased bleeding related to uremic platelet dysfunction can be managed by the administration of desmopressin, cryoprecipitate, or estrogens, and by avoiding the use of medications with antiplatelet effects close to the time of surgery. Transfusions of red blood cells should be reserved for use in patients with clinically significant anemia, because antibody formation may decrease the likelihood of successful renal transplantation in the future. Cardiovascular disease is the most common cause of death in patients with renal disease. Patients with chronic kidney disease may have hypertension and hypoglycemia in the perioperative period. Preoperative testing may be necessary in patients with cardiac risk factors. If future vascular access grafting is contemplated, intravenous line placement and blood draws should be avoided in a patient's nondominant arm.
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PMID:Preoperative care of patients with kidney disease. 1240 21

A role for the sympathetic nervous system in hypertension has been looked for in relation to the 'metabolic syndrome' with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin-induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2-deoxy-D-glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change. After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C-peptide-negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure. A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipose tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the 'metabolic syndrome' and hypertension.
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PMID:Sympathetic nerve activity in metabolic control--some basic concepts. 1260 4

We previously demonstrated that left ventricular hypertrophy (LVH) induced by angiotensin II infusion requires epidermal growth factor receptor (EGFR) activation to mediate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. To test whether the EGFR-mediated MAPK/ERK activation plays an important role in development and maintenance of LVH in spontaneously hypertensive rats (SHR), we investigated the effects of antisense oligodeoxynucleotide to EGFR (EGFR-AS) on LVH and blood pressure in young and adult SHR. EGFR-AS, sense oligonucleotide to EGFR (EGFR-S; 1.5 mg/kg), or vehicle control (5% dextrose) with liposome was injected once a week for 2 months in 5- or 13-week-old SHR. The effect of EGFR-AS on the expression of EGFR and phosphorylated ERK in the heart were examined by Western blots. After treatment, EGFR-AS significantly (P<0.05) decreased left ventricular weight/body weight and blood pressure in young SHR compared with EGFR-S or control-treated rats. In adult SHR, EGFR-AS did not affect left ventricular weight/body weight and blood pressure. EGFR and phosphorylated ERK significantly declined from 5 to 20 weeks (P<0.05). EGFR-AS, but not EGFR-S, significantly (P<0.05) decreased the expression of EGFR and phosphorylated ERK in young SHR, but had no significant effect in adult SHR. These results suggests that EGFR-mediated ERK activation is critically important for LVH in young SHR. This may be related to the high levels of EGFR and phosphorylated ERK in young SHR, suggesting a critical role of the EGFR-activated ERK pathway in cardiovascular development but not in the maintenance of established LVH in adult SHR.
Hypertension 2003 Mar
PMID:Antisense to epidermal growth factor receptor prevents the development of left ventricular hypertrophy. 1262 3


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