Role of nitric oxide in the hemodynamic changes of sepsis

Lorente, José A.; Landín, Luis; Renes, Emilio; Pablo, Raúl de; Jorge, Pablo; Ródena, Elena; Liste, D.

doi:10.1097/00003246-199305000-00021

Cited by 114 publications

(38 citation statements)

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“…However, our data and the results of Lorente et al, (42) suggest that unselective NOS inhibitors may be deleterious for renal function in septic shock. A limited number of clinical studies using L-NMMA, L-NAME, NNLA, or Methylene blue (43) support this conclusion: despite the increase in MAP, accompanied by increased vascular resistance and a partial restoration of vascular reactivity to noradrenaline, favorable effects on survival were not reported.…”

Section: Discussionsupporting

confidence: 42%

Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat.

Heneka

Löschmann²,

Oßwald³

1997

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 42%

Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat.

Heneka

Löschmann²,

Oßwald³

1997

J. Clin. Invest.

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“…Besides this, L-arginine administration further stimulated alveolar and intravascular NO release in the lung, with a slight limitation of the increase in pulmonary arterial pressure and concomitant oedema formation (Schutte et al 1998). LArginine treatment produced systemic vasodilatation in normal sheep, whereas both systemic and pulmonary vasodilatation was observed in septic animals in the later phase of sepsis (Lorente et al 1993b(Lorente et al , 1999. However, data on survival are not uniform (Gonce et al 1990;Gianotti et al 1993;Yeh et al 2002).…”

Section: Sepsismentioning

confidence: 99%

Pros and cons of L-arginine supplementation in disease

et al. 2004

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The amino acid arginine and one of its metabolites NO have gathered broad attention in the last decade. Although arginine is regarded as a conditionally essential amino acid in disease, L-arginine supplementation in severe illness has not found its way into clinical practice. This might be due to the invalid interpretation of results from studies with immune-enhancing diets containing L-arginine amongst other pharmaconutrients. However, not much attention is given to research using L-arginine as a monotherapy and the possibility of the alternative hypothesis: that L-arginine supplementation is beneficial in disease. The present review will discuss data from studies in healthy and diseased animals and patients with monotherapy of L-arginine to come to an objective overview of positive and negative aspects of L-arginine supplementation in disease with special emphasis on sepsis, cancer, liver failure and wound healing.

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“…This activation of matrix metalloproteinases contributes to loss of normal tissue architecture, leading to pathologic conditions. Parenthetically, the nitrosative stress produced by iNOS activation may also induce endothelial dysfunction with impaired regulation of vascular tone as in septic shock (Julou-Schaeffer et al, 1990;Lorente et al, 1993;Landry and Oliver, 2001;Nandi et al, 2012). This could be in part due to uncoupling of eNOS (Münzel et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

A Novel and Potent Inhibitor of Dimethylarginine Dimethylaminohydrolase: A Modulator of Cardiovascular Nitric Oxide

Ghebremariam¹,

Erlanson²,

Cooke³

2013

J Pharmacol Exp Ther

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3,4, [1,2-c]- [1,3]benzothiazine], a heterocyclic iminobenzothiazine derivative, is a member of the Library of Pharmacologically Active Compounds (LOPAC) that is reported to possess antimicrobial and anti-inflammatory properties. In this study, we used biochemical assays to screen LOPAC against human dimethylarginine dimethylaminohydrolase isoform 1 (DDAH1), an enzyme that physiologically metabolizes asymmetric dimethylarginine (ADMA), an endogenous and competitive inhibitor of nitric oxide (NO) synthase. We discovered that PD 404182 directly and dosedependently inhibits DDAH. Moreover, PD 404182 significantly increased intracellular levels of ADMA in cultured primary human vascular endothelial cells (ECs) and reduced lipopolysaccharideinduced NO production in these cells, suggesting its therapeutic potential in septic shock-induced vascular collapse. In addition, PD 404182 abrogated the formation of tube-like structures by ECs in an in vitro angiogenesis assay, indicating its antiangiogenic potential in diseases characterized by pathologically excessive angiogenesis. Furthermore, we investigated the potential mechanism of inhibition of DDAH by this small molecule and found that PD 404182, which has striking structural similarity to ADMA, could be competed by a DDAH substrate, suggesting that it is a competitive inhibitor. Finally, our enzyme kinetics assay showed time-dependent inhibition, and our inhibitor dilution assay showed that the enzymatic activity of DDAH did not recover significantly after dilution, suggesting that PD 404182 might be a tightly bound, covalent, or an irreversible inhibitor of human DDAH1. This proposal is supported by mass spectrometry studies with PD 404182 and glutathione.

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Role of nitric oxide in the hemodynamic changes of sepsis

Cited by 114 publications

References 0 publications

Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat.

Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat.

Pros and cons of L-arginine supplementation in disease

A Novel and Potent Inhibitor of Dimethylarginine Dimethylaminohydrolase: A Modulator of Cardiovascular Nitric Oxide

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