Effective inhibition of nitric oxide production by aminoguanidine does not reverse hypotension in endotoxaemic rats

Metcalf, Kerstin; Jungersten, Lennart; Lisander, Björn

doi:10.1034/j.1399-6576.2002.460104.x

Cited by 14 publications

(12 citation statements)

References 32 publications

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“…Although tachycardia during shock has been observed in some studies [8,28], bradycardia has been observed by others [29,30]. In the present study, there was no observed change in HR during LPSinduced shock, providing no evidence that a change in sympathetic stimulation to the heart is responsible for the decrease in stroke volume.…”

Section: Discussioncontrasting

confidence: 52%

“…Several studies have demonstrated that the transient phase of in vivo hypotension observed during endotoxic shock is mediated via a pathway independent of nitric oxide or prostaglandin formation [7][8][9]. Recently, it has been observed that potassium channels activated in arterial smooth muscle cause hyperpolarization in vitro when exposed to LPS [4,6,18].…”

Section: Discussionmentioning

confidence: 99%

“…At this time, the factors involved with the activation of these channels have not been specifically identified. Other studies have shown that there is no correlation between this potassium channel activation and the production of nitric oxide or prostaglandins during the transient phase of endotoxic shock [7][8][9]. However, the substances in question are also quite likely to be derived from the vascular endothelium.…”

Section: Introductionmentioning

confidence: 98%

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Effect of Potassium Channel and Cytochrome P450 Inhibition on Transient Hypotension and Survival during Lipopolysaccharide-Induced Endotoxic Shock in the Rat

Clayton

LeDuc²,

Kelly³

2005

Pharmacology

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The purpose of this study was to determine whether inhibition of potassium channels or cytochrome P450 attenuates the transient phase of hypotension during endotoxic shock in vivo, and to determine whether these interventions improve the rate of survival. Male Sprague-Dawley rats were pretreated with saline (0.2 ml, i.v.), tetraethylammonium chloride (TEA 30 mg/kg; 0.2 ml, i.v.), proadifen (SKF-525 A; 50 mg/kg, i.p.) or ketoconazole (50 mg/kg, i.p.) and challenged with lipopolysaccharide (LPS; 20 mg/kg, i.p.). Changes in heart rate, mean (MAP), systolic (SP) and diastolic (DP) arterial pressures as well as survival rate were then monitored for 45 min. Potassium channel inhibition with TEA had no effect on LPS-induced hypotension at any time point compared with saline (maximal fall in MAP of 79 ± 18 and 80 ± 13 mm Hg, respectively). Pretreatment with proadifen or ketoconazole, inhibitors of cytochrome P450, significantly attenuated LPS-induced hypotension compared with saline (maximal fall in MAP of 34, 26 and 63% below baseline, respectively). This effect was evident in all arterial pressures measured, MAP, SP and DP. At 45 min, the survival rate in the saline group was 66%. Pretreatment with TEA significantly reduced survival rate to 50% and pretreatment with proadifen or ketoconazole improved survival to 100% (p < 0.05). These results suggest that an arachidonic acid metabolite produced by a cytochrome P450-catalyzed reaction may contribute to the transient phase of LPS-induced hypotension. However, these effects do not appear to be mediated through potassium channel activation.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Effect of Potassium Channel and Cytochrome P450 Inhibition on Transient Hypotension and Survival during Lipopolysaccharide-Induced Endotoxic Shock in the Rat

Clayton

LeDuc²,

Kelly³

2005

Pharmacology

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“…In these experiments, four TDS groups (aged-matched with the TDS study above) received one daily injection of either the selective iNOS inhibitor, aminoguanidine (AG; 50 mg/kg/day i.p. ; Metcalf et al 2002), the selective nNOS inhibitor, 7-nitroindazole (7-NI; 12.5 mg/kg/day i.p. ; Ikeda et al 1998), the steroid synthesis inhibitor, ketokonazole (KCZ; 24 mg/kg/day i.p.…”

Section: Treatment Groupsmentioning

confidence: 99%

Stress?restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

et al. 2003

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“…These observations were further strengthened when a recent study suggested that the anti-oxidant property of aminoguanidine might have an anti-aging effect on cultured fibroblasts [43]. Other roles of aminoguanidine include inhibiting nonenzymatic glycosylation [44], polyamine formation and NO production [45]. Though the medium used in our studies has 5.6 mM glucose (comparable to serum glucose levels), sequestration of epidermis from serum might mean that this level is still too high.…”

Section: Discussionmentioning

confidence: 69%

Optimization of filaggrin expression and processing in cultured rat keratinocytes

Chatterjea

Resing

Old

et al. 2011

Journal of Dermatological Science

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IntroductionIn normal mammalian epidermis, cell division and expression of keratins K5/K14 in the basal layer is followed by K1/K10, the keratin bundling protein filaggrin, and cornified envelope proteins such as involucrin and loricrin [1,2]. However, hyperproliferative epidermal cells can be motile and phagocytic, and can sustain cell division in the suprabasal layers. The hyperproliferative differentiation phenotype, seen during wound healing or in certain disease states results in production of keratins K6/K16, high levels of involucrin, and parakeratotic cornified cells [3,4].For elucidation of structures and functions of the different types of epidermal cells, keratinocyte culture models were developed [5].These models of epidermal differentiation are complicated by the phenotypic plasticity of keratinocytes. In the extreme, this is represented by the "activated or hyperproliferative" vs "normal" differentiation programs. These programs are superficially similar in that a stratified epidermis with cornified cells forms, but each involves the expression of different structural proteins [6]. It appears that these two pathways are not mutually exclusive, so that cells can express a mixed phenotype in some situations.Terminal differentiation in both phenotypes involves degradation or remodeling of phospholipids, cytoplasm, cell organelles, and the nonkeratin cytoskeletal components [7]. Little is understood about the regulatory mechanisms for initiation of these global degradative processes. Lysosomal breakdown and release of lysosomal proteinases to the cytosol is unlikely, as there is no evidence that the terminally differentiating cell has a decreased pH and lysosomal enzymes are not very active at neutral pH. In fact, a major # Corresponding author: Division of Dermatology, Box 356524, University of Washington, Seattle WA, 98195-6524, Phone: 206-543-5290, Fax: 206-543-2489, fleck@uw.edu. * Deceased § Present Address: University of North Carolina at Chapel Hill, Chapel Hill NC, 27599Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript J Dermatol Sci. Author manuscript; available in PMC 2012 January 1. The enzymes responsible for specific processes in terminal differentiation have been shown to have neutral pH optima. For example, the cross-linking of proteins at the internal cytosolic face during formation of the cornified cell envelope involves a transglutaminase having a neutral pH optimum [9]. Proteolytic processing of profilaggrin in normal terminal differentiation apparently also involves a chymotrypsin-like proteinase having a neu...

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Effective inhibition of nitric oxide production by aminoguanidine does not reverse hypotension in endotoxaemic rats

Abstract: AG inhibited NO formation in a dose-dependent way. Yet, AG had no haemodynamic effects, suggesting a minor cardiovascular influence of iNOS in this endotoxin model, in parallel to what has been found in microbial sepsis.

Cited by 14 publications

References 32 publications

Effect of Potassium Channel and Cytochrome P450 Inhibition on Transient Hypotension and Survival during Lipopolysaccharide-Induced Endotoxic Shock in the Rat

Effect of Potassium Channel and Cytochrome P450 Inhibition on Transient Hypotension and Survival during Lipopolysaccharide-Induced Endotoxic Shock in the Rat

Stress?restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

Optimization of filaggrin expression and processing in cultured rat keratinocytes

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