Role of nitric oxide in maintaining vascular integrity in endotoxin‐induced acute intestinal damage in the rat

Hutcheson, Iain Robert; Whittle, Brendan J.R.; Boughton‐Smith, N. K.

doi:10.1111/j.1476-5381.1990.tb14163.x

Cited by 357 publications

(114 citation statements)

References 31 publications

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“…The apparently opposing effects of NO in vitro make it difficult to predict the biological effects of NO because its role may vary with differences in the tissue in which the inflammation occurs [38][39][40][41], differences in the presence of other pro-inflammatory or anti-inflammatory molecules, and its concentration or rate of delivery in the tissue [42]. The possibility that NO production by muscle can influence the occurrence of muscle injury and inflammation has been suggested by the observation that mdx mouse muscles, which express very low levels of NOS [43,44], experience extensive muscle inflammation and necrosis [45,46].…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Pizza

Hernandez

Tidball

1998

Journal of Leukocyte Biology

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The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with watertreated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

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Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Pizza

Hernandez

Tidball

1998

Journal of Leukocyte Biology

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“…Experimental studies using NOS inhibitors have also revealed ambivalent findings. Although several reports in animal models of sepsis have demonstrated an improvement in blood pressure, blocking NOS activity decreases renal blood flow, increases capillary leak and intestinal damage, and exacerbates pulmonary hypertension (21,22).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Role of nitric oxide in inflammation and tissue injury during endotoxemia and hemorrhagic shock.

Shah

Billiar

1998

Environ Health Perspect

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Since the discovery that nitric oxide ('NO) accounts for the biologic activity of endothelial-derived relaxing factor, a torrent of research over the last decade has focused on its role, protective or detrimental, in myriad pathophysiologic conditions. Recently, increasing attention has focused on 'NO as a possible mediator of the severe hypotension and impaired vasoreactivity characteristic of circulatory failure. Given the ubiquitous and complex role of 'NO in biologic systems, inhibition of 'NO synthesis in experimental and clinical studies of shock has yielded mixed, sometimes contradictory, results. Although overproduction of 'NO in the vasculature may result in systemic vasodilatation, 'NO synthesis has also clearly been shown to have a beneficial role in regulating organ perfusion and mediating cytotoxicity. In this review, the pathophysiologic importance of 'NO in septic shock and hemorrhagic shock is discussed, and novel therapeutic strategies for manipulation of 'NO formation are examined.

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“…However, the administration of NOS inhibitors, which are not selective for the inducible isoforms of NOS, also causes a concomittant inhibition of the constitutive NOS in the endothelium and may increase the incidence of organ ' Author for correspondence. ischaemia, microvascular thrombosis and mortality (Hutcheson et al, 1990;Harbrecht et al, 1992;Shultz & Raij, 1992;Wright et al, 1992). Moreover, the non-selective NOS inhibitor N0-nitro-L-arginine methyl ester (L-NAME) causes detrimental haemodynamic effects in pigs with septic shock (Robertson et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

Klemm¹,

Thiemermann

Winklmaier³

et al. 1995

British J Pharmacology

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1 The present investigation compares the effects of intravenous infusion of the NO synthase inhibitor NG-monomethyl-L-argiine (L-NMMA) with that of an inhalation with NO gas in a porcine model of endotoxin (lipopolysaccharide, LPS) shock. In addition, the effects of the combination of these two treatments were also investigated. 2 Male pigs were anaesthetized and instrumented for the measurement of haemodynamic parameters. Blood samples were withdrawn at different time intervals for determination of blood gases, pH, and plasma levels of nitrite/nitrate and tumour necrosis factor. 3 Endotoxin infusion (15 tLg kg-' h-' for 3 h) caused a progressive fall in mean arterial blood pressure (MABP) and cardiac output (CO) and a biphasic increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistence (PVR). A continuous infusion of L-NMMA (0.1 mg kg' min-') significantly attenuated the fall in MABP, but did not affect MPAP, CO and PVR. NO-inhalation (50 p.p.m.) did not affect MABP, but significantly blunted the biphasic increase in MPAP and PVR and significantly delayed the fall in CO. The combination of L-NMMA infusion (0.1 mg kg-' min-') with NO-inhalation (50 p.p.m.) completely prevented the fall in MABP, significantly improved CO, and attenuated the biphasic increase in MPAP and PVR. 4 %Endotoxin also caused a decline in Pao2 and a rise of Paco2. Infusion of L-NMMA neither affected the fall in Pao2 nor the increase in Paco2. In contrast, inhalation with NO gas alone as well as the combined administration of L-NMMA infusion and NO-inhalation completely prevented the fall in Pao2 and significantly protected against the increase in Paco2. 5 Infusion of endotoxin for 180 min resulted in a mortality of 58%, which was not affected by L-NMMA (63%). In contrast, treatment of LPS-animals with either NO-inhalation alone or NOinhalation plus L-NMMA completely prevented mortality. 6 This investigation demonstrates that treatment with NO-inhalation, in order to prevent the dramatic increase in MPAP, PVR and the alterations in peripheral blood gases combined with systemic L-NMMA to improve systemic MABP and thus organ perfusion, may be a new therapeutic regimen in the treatment of septic shock.

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Role of nitric oxide in maintaining vascular integrity in endotoxin‐induced acute intestinal damage in the rat

Cited by 357 publications

References 31 publications

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Role of nitric oxide in inflammation and tissue injury during endotoxemia and hemorrhagic shock.

Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock

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