Central but not systemic inhibition of inducible nitric oxide synthase modulates oxytocin release during endotoxemic shock

Stabile, Angelita Maria; Moreto, Viviana; Antunes‐Rodrigues, José; Cárnio, Evelin Capellari

doi:10.1016/j.peptides.2009.11.004

Cited by 14 publications

(22 citation statements)

References 41 publications

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“…aminoguanidine, appear to attenuate endotoxin-induced multiple organ dysfunction. It needs however to be determined precisely at what point during sepsis such selective inhibitors should be administered and their relative ability to selectively inhibit iNOS rather than cNOS is to be assumed (Parratt 1998;Stabile et al 2010).…”

Section: Resultsmentioning

confidence: 99%

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

Bauer¹,

Sotníková²

2010

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133

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Abstract. Vascular endothelium plays a key role in the local regulation of vascular tone and vascular architecture by release of vasodilator and vasoconstrictor substances, as well as factors with pro-coagulant, anticoagulant, fibrinolytic, antibacterial properties, growth factors, chemokines, free radicals, etc. Release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins and endothelium-derived hyperpolarizing factor, as well as vasoconstricting factors such as endothelin, superoxide and thromboxanes play an influential role in the maintenance and regulation of vascular tone and the corresponding peripheral vascular resistance. Under physiological conditions, the release of anticoagulant and smooth muscle relaxing factors exceeds the release of other substances. The first part of this review presents the functions of the endothelium itself, the nature of the endothelium-derived relaxing factor, its production by NO synthases, mechanisms of its action via activation of soluble guanylyl cyclase and production of cyclic 3'-5'-guanosine monophosphate. The resulting biological effects include vasodilatation, regulation of vessel wall structure, increased regional blood perfusion, lowering of systemic blood pressure, antithrombosis and antiatherosclerosis effects, which counteract the vascular actions of endogenous vasoconstrictor substances. Impaired endothelial function, either as a consequence of reduced production/release or increased inactivation of endothelium-derived vasodilators, as well as interactions of NO with angiotensin, reactive oxygen species and oxidized lipoproteins, has detrimental functional consequences and is one of the most important cardiovascular risk factors. Therefore the second part of this review assesses the pathophysiologic impact of the endothelium in examples of cardiovascular pathologies, e.g. endotheliopathies caused by increased angiotensin production, lipid peroxidation, ischemia/reperfusion or diabetes.

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Section: Resultsmentioning

confidence: 99%

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

Bauer¹,

Sotníková²

2010

gpb

133

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“…Besides its very well-known role in female physiology, in labor and lactation, OXT also contributes to cardiovascular regulation, feeding and gastric distension, body temperature and certain behaviors [9,10]. Although there are no clinical reports during sepsis regarding OXT secretion, an increase followed by a decrease in plasma OXT levels is observed during shock experimentally induced by lipopolysaccharide (LPS) [11,12]. Its secretory profile during polymicrobial sepsis has, however, not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Affects Nitric Oxide and Cytokine Production by Sepsis-Sensitized Macrophages

Oliveira-Pelegrin

Saia²,

Cárnio

et al. 2012

Neuroimmunomodulation

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Background/Aim: Oxytocin (OXT) secretion during cecal ligation puncture (CLP)-induced sepsis has not yet been examined. Although immune properties have been attributed to OXT, its effect on CLP-sensitized macrophages has never been investigated. We analyzed OXT secretion during CLP and its effect in CLP-sensitized macrophage cultures. Methods: Male Wistar rats were decapitated 4, 6 or 24 h after CLP surgery or sham operation and blood, brain and neurohypophyses were collected for OXT measurements. In another set of animals we studied the effect of OXT on nitrite, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-10 production of peritoneal macrophages harvested at 6 and 24 h after CLP. Results: In the early phase of sepsis (4–6 h), OXT levels increased in plasma and decreased in hypothalamus and neurohypophysis. In the late phase (24 h), plasma and neurohypophyseal levels remained basal. In the paraventricular, the OXT content remained low, but in the supraoptic increased. Macrophages of the early phase of sepsis pretreated with OXT and stimulated with lipopolysaccharide showed decreased nitrite, TNF-α and IL-1β levels, but no alteration in IL-10 production. In the late phase, they showed reduction only on IL-1β. Conclusions: OXT secretion during sepsis may represent a neuroendocrine response contributing to the overall host response to infection by decreasing the proinflammatory response and oxidative stress.

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“…[11][12][13] Pretreatment with iNOS Inhibitor The rats were pretreated with a selective iNOS inhibitor, aminoguanidine (AG) (Sigma Aldrich, Tokyo, Japan). The rats were injected (intravenously) with 100 mg/kg 13,17,18) AG dissolved in 1 ml of physiological saline (0.9% NaCl) for 5 min before ischemia. Rats that were not administered AG were intravenously injected with 1 ml of physiological saline (0.9% NaCl) 5 min before ischemia.…”

Section: Methodsmentioning

confidence: 99%

Effect of Aminoguanidine on Ischemia/Reperfusion Injury in Rat Small Intestine

Takizawa

Kitazato

Ishizaka

et al. 2011

Biological & Pharmaceutical Bulletin

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Ischemia/reperfusion (I/R) injury is induced by reactive oxygen species (ROS). During intestinal I/R, the amount of nitric oxide (NO), which is a ROS, is increased. In this study, we examined the protection against I/R injury by inhibition of NO generation. Wistar/ST rats were exposed to 1 h of ischemia, followed by reperfusion for 4 h. The rats were intravenously injected with 100 mg/kg aminoguanidine (AG), which is a selective inducible NO synthase (iNOS) inhibitor, for 5 min before ischemia. The increase in NO(2)(-) by intestinal I/R was significantly inhibited by AG 1 h after reperfusion. Moreover, the increase in area under curve of 0 to 1 h after reperfusion (AUC(0-1)) of paracellular marker was inhibited. However, 3 h after reperfusion, the survival ratio of rats was significantly decreased in the intestinal I/R condition with AG. The amount of NO(2)(-) and AUC of 3 to 4 h after reperfusion (AUC(3-4)) of paracellular marker in intestinal I/R groups were increased by AG compared with those in the I/R condition without AG 3 h after reperfusion. These data indicated that AG, which was given by single pre-administration, can clearly inhibit intestinal I/R injury 1 h after reperfusion. However, the injury occurs again 3 h after reperfusion and grows worse.

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Central but not systemic inhibition of inducible nitric oxide synthase modulates oxytocin release during endotoxemic shock

Cited by 14 publications

References 41 publications

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

Oxytocin Affects Nitric Oxide and Cytokine Production by Sepsis-Sensitized Macrophages

Effect of Aminoguanidine on Ischemia/Reperfusion Injury in Rat Small Intestine

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