l-Arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate

Mizuno, Tomohiro; Watanabe, Masahiro; Sakamoto, Tohru; Sunamori, M

doi:10.1016/s0022-5223(98)70376-9

Cited by 23 publications

(12 citation statements)

References 26 publications

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“…inflammatory response by compensating the reduced NO production from ecNOS. 35 The efficacy of NO supplementation has been demonstrated, 36,37 and we have demonstrated that selective iNOS inhibition aggregates CPB-induced inflammation. 28 Therefore, enhanced NO production is considered an adaptive response and a key process for attenuating the development of this response.…”

Section: Discussionmentioning

confidence: 82%

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

et al. 2002

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Background-Heat-shock protein 70 (HSP70) plays a major role in the pathophysiology of inflammation, and the induction of HSP70 before the onset of inflammation can reduce organ damage through a self-protective system. Glutamine is known to be an inducer of HSP70, and its preoperative administration seems useful in attenuating cardiopulmonary bypass (CPB)-induced inflammatory response. Methods and Results-Adult male Sprague-Dawley rats (group G, received 100 mg/kg of glutamine via the right jugular vein 3 times per day for 1 week and just before the initiation of CPB; group C served as control) underwent CPB (60 minutes, 100 mL/kg per minute, 34°C) and were killed 3 hours after the termination of CPB. Group G showed significantly lower plasma concentrations of interleukin-6 and interleukin-8 after CPB termination. Myocardial and respiratory damages were significantly attenuated in group G, as evidenced by Langendorff perfusion, respiratory index, and neutrophil adherence. HSP70 expressions in the heart, lung, and liver were detected only in group G before CPB and were markedly stronger in group G 3 hours after CPB termination. Although plasma nitrateϩnitrite concentrations were not significantly different between the groups, endothelial-constitutive nitric oxide synthase (NOS) activity was markedly preserved and inducible NOS activity was markedly attenuated in the tissues of group G. Conclusions-These results suggest that preoperative glutamine administration induces HSP70 expression before CPB and attenuates CPB-induced inflammation by regulating NOS activity, which may be a prospective management for conferring tolerance to CPB-induced inflammatory response through a self-protective mechanism. (Circulation. 2002; 106:2601-2607.)

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Section: Discussionmentioning

confidence: 82%

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

et al. 2002

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“…The mechanisms of NO in modulating cardiac function during I/R injury proposed in those studies are quite numerous. NO has been reported to exert multiple beneficial effects: inhibiting inositol-1,4,5-triphosphate and reducing calcium overload, 14 mediating protein kinase C translocation, 19 and inhibiting neutrophil-associated injury. 20 On the contrary, NO also has been reported to react with superoxide to form peroxynitrite, which is considered cytotoxic.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Myocardial Ischemia/Reperfusion Injury by Superinduction of Inducible Nitric Oxide Synthase

et al. 2000

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Background-Nitric oxide (NO) has been implicated as a mediator in myocardial ischemia/reperfusion (I/R) injury, but its functional properties have been conflicting. We investigated whether NO has a protective role against I/R injury. Methods and Results-Using endothelial NO synthase knockout (eNOS KO) mice, inducible NOS KO mice, the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), we performed studies of isolated perfused hearts subjected to 30 minutes of global ischemia followed by reperfusion. After 60 minutes of reperfusion, nitrite levels in the coronary effluent in the SNAP and eNOS KO groups were significantly elevated compared with other groups. Immunoblot and immunohistochemistry showed that iNOS was markedly induced in the eNOS KO hearts. Under spontaneous beating conditions during reperfusion, increased NO activity was correlated with a prevention of the hyperdynamic contractile response and enhanced myocardial protection, as evidenced by a reduction in myocardial injury and infarct size. During prolonged reperfusion, SNAP-treated hearts were able to preserve contractile functions for 180 minutes, whereas L-NIO-treated hearts showed a sustained deterioration in contractility. Conclusions-NO protects against I/R injury by preventing the hyperdynamic response of isolated perfused hearts during early reperfusion. In the eNOS KO hearts, a paradoxical increase in NO production was seen, accompanied by a superinduction of iNOS, possibly due to an adaptive mechanism.

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“…Under our experimental conditions, it was not possible to determine differences in cardiac function between D-or Larginine-treated hearts, despite a slight increase in postischemic peak LEDVP and a decrease in heart rate. Many authors have described beneficial effects of L-arginine treatment on the recovery of myocardial function during reperfusion (Engelman et al, 1996;Brunner et al, 1997;Wang et al, 1997;Mizuno et al, 1998;Padilla et al, 2000), whereas others have shown a harmful effect of L-arginine administration (Takeuchi et al, 1995;Mori et al, 1998). These discrepancies can be attributed to different experimental models but also to the critical timing of this amino acid administration.…”

Section: Tablementioning

confidence: 99%

“…These discrepancies can be attributed to different experimental models but also to the critical timing of this amino acid administration. In fact, L-arginine seems even more powerful as a pretreatment (Engelman et al, 1996;Wang et al, 1997;Mizuno et al, 1998), and sometimes deleterious during reperfusion (Takeuchi et al, 1995;Engelman et al, 1996). Therefore, the absence of functional parameters' variations between D-or L-arginine observed under our experimental conditions might be the addition of both beneficial and detrimental effects of L-arginine administration.…”

Section: Tablementioning

confidence: 99%

“…All three isoforms of NOS may be expressed in the heart (for review, see Shah and MacCarthy, 2000), albeit in a cell-specific manner, and the numerous physiological effects of ⅐ NO on cardiac function have been reviewed (Kelly et al, 1996). During myocardial reperfusion, the role of ⅐ NO in the development of myocardial injury has been extensively studied in different experimental models, using either NOS antagonists (Depré et al, 1995;Naseem et al, 1995;Zweier et al, 1995;Wang and Zweier, 1996;Brunner et al, 1997;du Toit et al, 1998;Zhang et al, 2001), L-arginine (Takeuchi et al, 1995;Engelman et al, 1996;Brunner et al, 1997;Wang et al, 1997;Mizuno et al, 1998), ⅐ NO donors (Brunner et al, 1997;du Toit et al, 1998), or NOS-knockout mice models (Flögel et al, 1999;Kanno et al, 2000). However, there are contradictory results concerning the possible protective or deleterious role of ⅐ NO during ischemia and reperfusion.…”

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confidence: 99%

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Postischemic Recovery and Oxidative Stress Are Independent of Nitric-Oxide Synthases Modulation in Isolated Rat Heart

Vergely¹,

Perrin-Sarrado²,

Clermont³

et al. 2002

J Pharmacol Exp Ther

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During myocardial ischemia and reperfusion, nitric oxide ( ⅐ NO) was shown to exert either beneficial or detrimental effects. Uncoupled ⅐ NO synthases (NOS) can generate superoxide anion under suboptimal concentrations of substrate and cofactors. The aim of our study was to investigate the role of NOS modulation on 1) the evolution of functional parameters and 2) the amount of free radicals released during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 30 min of total ischemia, followed by 30 min of reperfusion in the presence of N G -nitro-D-or L-arginine methyl ester (NAME, 100 M) or of D-or L-arginine (3 mM). Functional parameters were recorded and coronary effluents were analyzed with electron spin resonance to identify and quantify the amount of ␣-phenyl-N-tert-butylnitrone spin adducts produced during reperfusion.The antioxidant capacities of the compounds were determined with the oxygen radical absorbance capacity test. L-NAMEtreated hearts showed a reduction of coronary flow and contractile performance, although neither L-NAME nor L-arginine improved the recovery of coronary flow, left end diastolic ventricular pressure, rate pressure product, and duration of reperfusion arrhythmia, compared with their D-specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals was detected upon reperfusion, but no differences of free radical release were observed between D-and L-NAME or D-and L-arginine treatment. These results may indicate that, in our experimental conditions, cardiac NOS might not be a major factor implicated in the oxidative burst that follows a global myocardial ischemia.

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l-Arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate

Abstract: These data suggest that L-arginine pretreatment may reduce calcium overload by increasing cyclic guanosine monophosphate production, which in turn downregulates inositol triphosphate synthesis during reperfusion.

Cited by 23 publications

References 26 publications

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass–Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity

Attenuation of Myocardial Ischemia/Reperfusion Injury by Superinduction of Inducible Nitric Oxide Synthase

Postischemic Recovery and Oxidative Stress Are Independent of Nitric-Oxide Synthases Modulation in Isolated Rat Heart

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