Nitric Oxide and Cardiovascular Dysfunction in Sepsis and Endotoxaemia: An Introduction and an Overview

Parratt, J. R.

doi:10.1007/978-3-642-79343-1_1

Cited by 9 publications

(6 citation statements)

References 63 publications

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“…This is even more pronounced following endotoxin administration than it is under normal conditions, as originally suggested by Tesfamarian et al (1987) and by Thorin & Atkinson (1994). We suggest that this impairment of neurogenically invoked vasoconstriction contributes to the vasoplegia and unrelenting systemic hypotension which is characteristic of animals administered endotoxin and of patients with sepsis (reviewed by Parratt, 1995).…”

Section: Discussionsupporting

confidence: 71%

The effect of endotoxin on sympathetic responses in the rat isolated perfused mesenteric bed; involvement of nitric oxide and cyclo‐oxygenase products

Fatehi‐Hassanabad

Furman

Parratt

1995

British J Pharmacology

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1 The effects of endotoxin on the vasoconstrictor responses to sympathetic nerve stimulation (SNS) were investigated in the rat isolated perfused mesenteric bed. 2 Rats received either saline (0.1 ml h-') or endotoxin (2.5 mg kg-' h-') intravenously for 4 h; the mesenteric beds were then isolated, perfused with Krebs and prepared for SNS (50 V, 3 ms,. 3 SNS caused a frequency-dependent vasoconstrictor response which was abolished by either tetrodotoxin (10-7 M), prazosin (2.4 x 10-7M) or guanethidine (2.4 x 10-7 M). 7 Both L-NAME (10-3 M) and indomethacin (10-5 M) restored responses to SNS in preparations from endotoxin-treated rats without modifying these responses in control preparations. However, coadministration of L-NAME and indomethacin markedly augmented responses in both control and endotoxin-treated preparations.8 The effects of L-NAME were reversed by addition of L-arginine (10-3 M). 9 The data suggest that endotoxin impairs the release of noradrenaline and that this effect is secondary to increased production of nitric oxide and prostanoids, possibly by the endothelium.

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Section: Discussionsupporting

confidence: 71%

The effect of endotoxin on sympathetic responses in the rat isolated perfused mesenteric bed; involvement of nitric oxide and cyclo‐oxygenase products

Fatehi‐Hassanabad

Furman

Parratt

1995

British J Pharmacology

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“…These NO concentrations were 60Ϯ4, 68Ϯ3, 70Ϯ4, 67Ϯ4, and 65Ϯ3 nmol/L above the basal level for 1, 2, 3, 4, and 6 hours, respectively. However, the estimated concentration of NO measured indirectly by NO 2 Ϫ /NO 3 Ϫ assay in blood plasma by the Griess method 9 increased linearly within this time interval (1.3Ϯ0.1, 1.7Ϯ0.2, 2.4Ϯ0.2, 3.6Ϯ0.3, and 5.8 mol/L for 1, 2, 3, 4, and 6 hours, respectively).…”

Section: No Releasementioning

confidence: 91%

“…1 The signal to transcribe/translate the gene sequence for iNOS can be transmitted by several endotoxins, including LPS. 3 In rodents, iNOS expression occurs mainly in macrophages, but it also occurs in several other cell types, including endothelial cells. 4 Clinically, L-NNA or a number of other L-arginine analogues, which are unable to differentiate between the inhibition of iNOS and cNOS, were used for the treatment of septic shock patients with encouraging results.…”

mentioning

confidence: 99%

Protective Role of Pulmonary Nitric Oxide in the Acute Phase of Endotoxemia in Rats

Gryglewski

Wołkow

Uracz

et al. 1998

Circulation Research

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We present for the first time direct continuous assay of NO concentration (porphyrinic sensor) in the lung parenchyma of Sprague-Dawley rats in vivo during endotoxemia. Intravenous infusion of lipopolysaccharide (LPS, 2 mg x kg(-1) x min(-1) for 10 minutes) stimulated an acute burst of NO from constitutive NO synthase (NOS) that peaked 10 to 15 minutes after the start of LPS infusion, mirroring a coincident peak drop in arterial pressure. NO concentration declined over the next hour to twice above pre-LPS infusion NO levels, where it remained until the rats died, 5 to 6 hours after LPS infusion. The chronic drop in arterial pressure observed from 70 minutes to 6 hours after the start of LPS infusion was not convincingly mirrored by a chronic increase in NO concentration, even though indirect NO assay (Griess method, assaying NO decay products NO2-/NO3-) showed that NO production was increasing as a result of continuous NO release by inducible NOS. A NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.) injected 45 minutes before LPS infusion, resulted in sudden death accompanied by macroscopically/microscopically diagnosed symptoms similar to acute respiratory distress syndrome <25 minutes after the start of LPS infusion. Pharmacological analysis of this L-NNA+LPS model by replacing L-NNA with 1-amino-2-hydroxy-guanidine (selective inhibitor of inducible NOS) or by pretreatment with S-nitroso-N-acetyl-penicillamine (NO donor), camonagrel (thromboxane synthase inhibitor), or WEB2170 (platelet-activating factor receptor antagonist) indicated that in the early acute phase of endotoxemia, LPS stimulated the production of cytoprotective NO, cytotoxic thromboxane A2, and platelet-activating factor.

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“…Removing L-arginine this last enzyme decreases generation of NO by iNOS (23). (21). Successful treatment of experimental endotoxaemia with L-NMMA Q4) was followed by its clinical use in septic shock patients (25).…”

mentioning

confidence: 99%

Crossroads of L-Arginine/Arachidonate Metabolism

et al. 1997

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Nitric oxide (NO) and prostacyclin (PGI, or prostaglandins (e.g., PGE) disclose a couple of biological similarities. The substrates for their biosynthesis [L-arginine (L-Arg) or arachidonate (AA)] abide structural peptides or phospholipids. Hydrolysis is required to present the zubstrates to corresponding diorygenases, i.e., NO synthase (NOS) or PGH synthase (PGHS) with its cyclooxygenase (COX) subunit. Both NOS and COX exist in their constinrtive (e.g., ecNOS, COX-I) or inducible (iNOS, COX-2) isoforms. Transcription of iNOS and COX-2 is triggered by cytokines or endotoxin (lipopolysaccharide from Escherichia coli, LPS). The endothelial constitutive enzymes release NO and PGI2 in a coupled manner (1,2). These endothelial mediators execute their cytoprotective firnctions through cyclic nucleotides, i.e., cyclic-GMP and cyclic-AMP, respectively. Some other eicosanoids, e.9., Coxderived thromboxane A2 (TXAz) or 5-lipoxygenasederived cysteinyl-letrkotrienes (e.9., LTCa) are cytotoxic just like NO might be (1 ,2). Free radicals are essential for the performance of NO and eicosanoids. For instance, superoxide anion (Ot) reveals its hidden cytotoxicity by making peroxynitrite (ONOO-) of NO. Peroxynitrite is the only generator of biogenic nitrotyrosine Q,4); it is an activator of polyadenosinediphosphateribose synthase (PARS) atrd, thereby, a depletor of cellular energy (5). It initiates membrane lipid peroxidation (6) and depletes intracellular glutathione (7). There is an ample evidence for differential biological activities of NO and ONOO-(8). NO seelns to be responsible for physiological cyclic-GMP-mediated responses while ONOO-covers pathology ascribed to NO unless thiols (e.9., cysteine or glutathione) will break peroxynitrite to a benignant S-nitrosothiol (9). Hydroxyl radical is essential for oxygenation of AA by COX, while various lipid peroxides intribit PGI, synthase (1 ,2). Among L-ArglAA crossroads the least known is an interaction at a level of NOS and COX. NO was claimed to inhibit COX (10); however, the real executor seeilN to be ONOO-, uls in the case of PGI2 synthase (11).

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Nitric Oxide and Cardiovascular Dysfunction in Sepsis and Endotoxaemia: An Introduction and an Overview

Cited by 9 publications

References 63 publications

The effect of endotoxin on sympathetic responses in the rat isolated perfused mesenteric bed; involvement of nitric oxide and cyclo‐oxygenase products

The effect of endotoxin on sympathetic responses in the rat isolated perfused mesenteric bed; involvement of nitric oxide and cyclo‐oxygenase products

Protective Role of Pulmonary Nitric Oxide in the Acute Phase of Endotoxemia in Rats

Crossroads of L-Arginine/Arachidonate Metabolism

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