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  • 1
    Electronic Resource
    Electronic Resource
    Cyclosporin-induced endothelial dysfunction and hypertension: are nitric oxide system abnormality and oxidative stress involved? (2000)
    Springer
    Transplant international 13 (2000), S. S413 
    Details
    ISSN: 1432-2277
    Keywords: Key words ecNOS ; Nitric oxide ; Cyclosporine ; Hypertension ; Superoxide anions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hypertension is a major side effect of cyclosporin (CsA). While the mechanism(s) responsible are unclear, CsA-induced endothelial dysfunction and CsA-induced hypertension have been attributed to the CsA effect on the endothelial-derived factors controlling vasomotor tone. Endothelial nitric oxide (NO) is crucial in the maintenance of a state of basal vasodilation, and recent studies have suggested an NO-mediated counterregulatory mechanism protective from CsA-induced vasoconstriction. Our study evaluates endothelial nitric oxide synthase (ecNOS) gene status (PCR analysis) and plasma levels of NO metabolites (ELISA) in kidney and heart transplant patients under chronic CsA treatment with CsA-induced hypertension. Since CsA increases superoxide production, which metabolises NO, plasma hydroperoxides from cholesterol esters and from triglycerides and peroxynitrite were also evaluated (HPLC) as an index of the presence of superoxides and of “oxidative stress”. Quantification of monocyte ecNOS mRNA and NO metabolites plasma levels from patients and controls (C) demonstrated NO system upregulation in patients notwithstanding the hypertension. The mean ecNOS to β-actin ratio was 1.80 ± 0.85 in patients vs 0.40 ± 0.09 in C (P 〈 0.04). NO metabolites were 34.03 ± 14.32 μM in patients vs 11.53 ± 5.64 μM in C (P 〈 0.001). Hydroperoxides from cholesterol esters and from triglycerides were also increased in patients, 3.4 ± 1.4 vs 1.3 ± 0.6 integrated area units (i. a. u.), P 〈 0.007 and 10.6 ± 6.4 vs 1.3 ± 0.8 i. a. u., P 〈 0.008, respectively, as well as the peroxynitrite plasma level, 0.32 ± 0.11 μM/l vs undetectable in C. This study confirms a CsA-induced NO system upregulation in transplanted patients. However, the NO-mediated counterregulatory system to CsA-induced vasoconstriction, present in normals, could be canceled in patients by CsA-induced superoxide (O2 –) and free radical production which, by increasing NO metabolism, could contribute to CsA-induced vasoconstriction and hypertension and predispose to atherosclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050374
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of doxazosin in mild to moderate hypertensive patients with insulin-dependent diabetes mellitus (1998)
    Springer
    Acta diabetologica 35 (1998), S. 96-100 
    Details
    ISSN: 1432-5233
    Keywords: Key words Insulin-dependent diabetes mellitus ; Hypertension ; Doxazosin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Diabetic patients often develop hypertension, and the presence of both hypertension and diabetes doubles the risk of death from coronary heart disease (CHD). Moreover, the presence and importance of abnormalities such as high low-density lipoprotein (LDL) cholesterol and triglycerides levels as CHD risk factors in insulin-dependent diabetes mellitus type 1 have been downplayed, while increasing evidence suggests that the management of type 1 patients should include control of dyslipidemia and hyperglycemia and an effective antihypertensive treatment able also to reduce risk factors for coronary artery events. In this study we assessed the antihypertensive and metabolic effects of doxazosin in hypertensive patients with type 1 diabetes. We show that the drug normalizes blood pressure, and while no improvement in glucose control was observed, it reduced total cholesterol and increased HDL cholesterol as well as the HDL to total cholesterol ratio. The changes of the various parameters studied, including the calculated CHD risk score based on the Framingham equation, suggest that doxazosine can reduce the CHD risk for hypertensive type 1 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050111
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Energy Metabolism of Synaptosomal Subpopulations from Different Neuronal Systems of Rat Hippocampus: Effect of L-Acetylcarnitine Administration In Vivo (1999)
    Springer
    Neurochemical research 24 (1999), S. 617-624 
    Details
    ISSN: 1573-6903
    Keywords: Synaptosomal subpopulations ; “large” and “small” synaptosomes ; energy metabolism ; enzymes ; L-acetylcarnitine treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The maximum rate (Vmax) of some enzyme activities related to glycolysis, Krebs' cycle, acetylcholine catabolism and amino acid metabolism were evaluated in different types of synaptosomes obtained from rat hippocampus. The enzyme characterization was performed on two synaptosomal populations defined as “large” and “small” synaptosomes, supposed to originate mainly from the granule cell glutamatergic mossy fiber endings and small cholinergic nerve endings mainly arising from septohippocampal fiber synapses, involved with cognitive processes. Thus, this is an unique model of pharmacological significance to study the selective action of drugs on energy metabolism of hippocampus and the sub-chronic i.p. treatement with L-acetylcarnitine at two different dose levels (30 and 60 mg · kg−1, 5 day a week, for 4 weeks) was performed. In control animals, the results indicate that these two hippocampal synaptosomal populations differ for the potential catalytic activities of enzymes of the main metabolic pathways related to energy metabolism. This energetic micro-heterogeneity may cause their different behaviour during both physiopathological events and pharmacological treatment, because of different sensitivity of neurons. Therefore, the micro-heterogeneity of brain synaptosomes must be considered when the effect of a pharmacological treatment is to be evaluated. In fact, the in vivo administration of L-acetylcarnitine affects some specific enzyme activities, suggesting a specific molecular trigger mode of action on citrate synthase (Krebs' cycle) and glutamate-pyruvate-transaminase (glutamate metabolism), but mainly of “small” synaptosomal populations, suggesting a specific synaptic trigger site of action. These observations on various types of hippocampal synaptosomes confirm their different metabolic machinery and their different sensitivity to pharmacological treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1021008306414
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  • 4
    Electronic Resource
    Electronic Resource
    Action of L-Acetylcarnitine on Different Cerebral Mitochondrial Populations from Cerebral Cortex (1998)
    Springer
    Neurochemical research 23 (1998), S. 1485-1491 
    Details
    ISSN: 1573-6903
    Keywords: Cerebral cortex ; energy metabolism ; enzymes ; L-acetylcarnitine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-acetylcarnitine at two different doses (30 and 60 mg·kg−1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic “light” and “heavy” ones. In fact, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and α-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1020907400905
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    Paper (German National Licenses)
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