Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of elevated D-glucose on adenosine transport were investigated in human cultured umbilical vein endothelial cells isolated from normal pregnancies. Elevated D-glucose resulted in a time- (8-12 h) and concentration-dependent (half-maximal at 10+/-2 mM) inhibition of adenosine transport, which was associated with a reduction in the Vmax for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside with no significant change in Km. d-Fructose (25 mM), 2-deoxy-D-glucose (25 mM) or D-mannitol (20 mM) had no effect on adenosine transport. Adenosine transport was inhibited following incubation of cells with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA; 100 nM, 30 min to 24 h). D-Glucose-induced inhibition of transport was abolished by calphostin C (100 nM, an inhibitor of PKC), and was not further reduced by PMA. Increased PKC activity in the membrane (particulate) fraction of endothelial cells exposed to D-glucose or PMA was blocked by calphostin C but was unaffected by NG-nitro-L-arginine methyl ester (L-NAME; 100 microM, an inhibitor of nitric oxide synthase (NOS)) or PD-98059 (10 microM, an inhibitor of mitogen-activated protein kinase kinase 1). D-Glucose and PMA increased endothelial NOS (eNOS) activity, which was prevented by calphostin C or omission of extracellular Ca2+ and unaffected by PD-98059. Adenosine transport was inhibited by S-nitroso-N-acetyl-l, d-penicillamine (SNAP; 100 microM, an NO donor) but was increased in cells incubated with L-NAME. The effect of SNAP on adenosine transport was abolished by PD-98059. Phosphorylation of mitogen-activated protein kinases p44mapk (ERK1) and p42mapk (ERK2) was increased in endothelial cells exposed to elevated D-glucose (25 mM for 30 min to 24 h) and the NO donor SNAP (100 microM, 30 min). The effect of D-glucose was blocked by PD-98059 or L-NAME, which also prevented the inhibition of adenosine transport mediated by elevated D-glucose. Our findings provide evidence that D-glucose inhibits adenosine transport in human fetal endothelial cells by a mechanism that involves activation of PKC, leading to increased NO levels and p42-p44mapk phosphorylation. Thus, the biological actions of adenosine appear to be altered under conditions of sustained hyperglycaemia.
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PMID:Regulation of adenosine transport by D-glucose in human fetal endothelial cells: involvement of nitric oxide, protein kinase C and mitogen-activated protein kinase. 1111 5

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.
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PMID:Impaired response to insulin associated with protein kinase C in chronic fructose-induced hypertension. 1252 77

The present work investigates the involvement of kinins in the effects of taurine in fructose-fed hypertensive rats. The effects of taurine on blood pressure, plasma glucose, insulin, and the insulin sensitivity index were determined. Angiotensin-converting enzyme (ACE) activity and nitrite content in plasma, plasma and tissue kallikrein activity, and taurine content were also investigated. The blood pressure changes in response to the coadministration of inhibitors of the synthesis of nitric oxide (NO), prostaglandins (PGs), or a kinin receptor blocker along with taurine was also evaluated. Fructose-fed rats had higher blood pressure and elevated plasma levels of glucose and insulin. Kallikrein activity, taurine, and nitrite contents were significantly lower in fructose-fed rats as compared with controls. The increases in systolic blood pressure, hyperglycemia, and hyperinsulinemia were controlled by taurine administration in fructose-fed rats. ACE activity was lower, while nitrite and taurine content and kallikrein activity were higher, in taurine-supplemented rats as compared with fructose-fed rats. A significant increase in blood pressure was observed in rats cotreated with the inhibitors Hoe 140 (a kinin receptor blocker), L-NAME (a NO synthase inhibitor), or indomethacin (a PG synthesis inhibitor) with taurine for 1 week as compared with taurine-treated fructose-fed rats. This suggests that the antihypertensive effect of taurine in fructose-fed rats was blocked by the inhibitors. Augmented kallikrein activity and, hence, increased kinin availability may be implicated in the effects of taurine in fructose-fed hypertensive rats.
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PMID:Potential role of kinins in the effects of taurine in high-fructose-fed rats. 1505 99

Recently we showed that the administration of intraperitoneal L-carnitine (CA) has insulin-sensitizing effects in the high fructose-fed Wistar rat, a widely used model of metabolic syndrome. The present study was conducted to examine the regulatory effects of CA on blood pressure (BP) and related pressor mechanisms. Fructose-fed rats (FFR) showed elevated BP, cardiac hypertrophy, glucose intolerance, and increases in plasma glucose, insulin, free fatty acids (FFA), and angiotensin-converting enzyme (ACE) activity. They also showed increased protein kinase C betaII (PKC betaII) expression and oxidative stress in cardiac tissue. In plasma, decreased kallikrein enzyme activity and nitric oxide metabolites were observed, compared to control. Simultaneous treatment with CA (300 mg/Kg) mitigated these alterations. PKC betaII expression was similar to that of control; the rats displayed normal BP and ACE activity, enhanced antioxidant protection, and close to normal values of metabolic parameters. The BP-lowering effect of CA was abolished when CA-treated rats were administered L-nitroarginyl methyl ester (L-NAME 6g/Kg). These observations suggest that the BP-lowering action of CA in this model could be attributed to multiple and interrelated mechanisms, such as an increase in NO and kinin availability, reduction in PKC action, and antioxidant protection.
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PMID:Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat. 1805 77

Previous studies show that naringenin promotes insulin sensitivity in fructose-fed rats. This study investigates whether naringenin prevents oxidative events and apoptotic changes triggered in the rat liver by a high fructose diet. Male Wistar rats of body weight 150-180 g were fed either diet containing starch (60% carbohydrate) or fructose (60% fructose diet). From the 16th day of feeding, rats in each dietary group were divided into two, and treated or not with naringenin (50mg/kg b.w/day). After 60 days, oxidative and nitrosative damage and endothelial nitric oxide synthase (eNOS) expression and hepatocyte apoptosis were determined. To evaluate whether nitric oxide (NO) plays a role in naringenin action, insulin sensitivity indices, fasting plasma glucose and insulin were assessed in response to co-administration of L-nitro-arginine methyl ester (L-NAME), a NOS inhibitor. Fructose feeding caused oxidative damage to proteins and lipids and resulted in reduced antioxidant status, eNOS expression and nitrite level. Increased formation of 4-hydroxy nonenal (4-HNE), 2, 4-dinitrophenol (2, 4-DNP) and 3-nitrotyrosine (3-NT)-modified proteins and the presence of apoptotic nuclei were observed in the liver. Treatment with naringenin attenuated all these parameters to levels not significantly different from control. Treatment with naringenin improved insulin sensitivity. However, L-NAME plus naringenin administration abolished the insulin-sensitizing effects of naringenin in fructose-fed rats. Reduced oxidative events with simultaneous increase in NO bioavailability may be involved in the insulin-sensitizing and cytoprotective effects of naringenin in fructose-fed rats.
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PMID:Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats. 2065

The prevalence of metabolic syndrome has increased in modern society and the condition is proving to be a common precursor of cardiovascular disease. The aim of the present study was to investigate whether astragaloside IV, a major active constituent of Astragalus membranaceus (Fisch) Bge., is able to prevent the development of hypertension and endothelial dysfunction in fructose-fed rats. Rats were fed with 10% fructose in their drinking water for 8 weeks. From the beginning of week 5, two groups of fructose-fed rats were treated with 0.5 or 2 mg/kg, i.p., astragaloside IV. Another group of fructose-fed rats, injected with the same volume of vehicle (dimethylsulfoxide, DMSO) from week 5, served as the control group. At the end of the treatment period, blood pressure, blood glucose, glucose tolerance, blood insulin and lipids were determined. In addition, in vitro experiments were conducted at the end of the eight week treatment period to evaluate endothelium-dependent aortic vasorelaxation, as well as myocardial and aortic tissue levels of nitrate and nitrite (NOx) and cGMP. Fructose-fed rats developed clustering signs of metabolic syndrome, such as increased bodyweight, mild hypertension, hyperinsulinaemia, hypertriglyceridaemia, impaired glucose tolerance and impaired endothelium-dependent vasorelaxation. Administration of astragaloside IV reduced blood pressure and triglyceride levels in fructose-fed rats and high dose of astragaloside IV also improved glucose tolerance and endothelium-dependent vasorelaxation. The astragaloside IV-induced improvement in vasorelaxation was associated with increased levels of aortic NOx and cGMP and was abrogated by blockade of nitric oxide synthase with NG-nitro-l-arginine methyl ester (l-NAME). On the basis of its favourable effects on lipid metabolism, endothelium-dependent vasorelaxation and the nitric oxide-cGMP-related pathway, astragaloside IV may be useful in ameliorating food-induced metabolic syndrome.
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PMID:Astragaloside IV improves metabolic syndrome and endothelium dysfunction in fructose-fed rats. 2155 78

The aim of this study was to evaluate the involvement of nitric oxide (NO) system damage in the deleterious effects of high-fructose intake in rats. Fructose was administered as 10% solution in drinking water to twelve-week-old male Wistar rats for the period of 8 weeks. Blood pressure was measured by tail-cuff plethysmography. After sacrificing the rats at the end of the treatment, relative weights of heart and liver and biochemical parameters in blood plasma were determined. Reactivity of isolated conduit arteries was measured using a force-displacement transducer for recording isometric tension. Fructose drinking rats had increased blood pressure and impaired acetylcholine-induced relaxation of the thoracic aorta in comparison with control rats drinking just tap water. Relative liver weight and plasma concentrations of glucose and triglycerides were also elevated after fructose administration. In a further group of Wistar rats, inhibition of NO production by administration of N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day) was performed throughout fructose intake. L-NAME treatment itself induces increase in blood pressure and relative heart weight as well as impairment in arterial relaxation and contractility. However, in these rats, fructose administration did not cause further elevation of blood pressure and other abnormalities observed in rats receiving fructose without L-NAME. Our results showed that in the state of NO deficiency (induced by L-NAME administration) fructose does not induce cardiovascular and metabolic alterations which develop in rats with a functional NO system. This indicates that impairment of the NO system may participate in many of the adverse effects induced by high-fructose intake.
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PMID:Cardiovascular effects of high-fructose intake in rats with nitric oxide deficiency. 2610 94

Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected.
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PMID:Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids. 2865 29