Aminoguanidine Inhibits Inducible NOS and Reverses Cardiac Dysfunction Late After Ischemia and Reperfusion - Implications for iNOS-Mediated Myocardial Stunning

Sm, Wildhirt; Schulze, C.; Conrad, Nicole; Kornberg, Arno; Horstman, Damian J.; Reichart, B.

doi:10.1055/s-2007-1013128

Cited by 23 publications

(14 citation statements)

References 27 publications

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“…Later studies (2,15,17,22,27,28) observed a gradual reappearance of protection within 24 h after the initial ischemic stimulus and with a longer duration of effect (3-4 days), which has been termed SWOP or the delayed phase of preconditioning. Several proteins have been identified as possible mediators of SWOP, including NOS, cyclooxygenase-2, ATP-sensitive K ϩ channels, antioxidant enzymes, and heat stress proteins (2,4,12,13,30). Considerable evidence (2,4,13,15,17,27,28,31) supports the concept that NO is a mediator of the SWOP in both coronary vessels and myocytes.…”

Section: Discussionmentioning

confidence: 99%

Enhanced iNOS function in myocytes one day after brief ischemic episode

Kim¹,

Kim²,

Takagi³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Vatner. Enhanced iNOS function in myocytes one day after brief ischemic episode. Am J Physiol Heart Circ Physiol 282: H423-H428, 2002; 10.1152/ajpheart.00609.2001.-There is increasing evidence that nitric oxide (NO) produced by inducible NO synthase (iNOS) plays a key role in cadioprotection during the "second window of protection" (SWOP). The goals of this study were to determine 1) whether a transient ischemic episode [10-min coronary artery occlusion (CAO), followed by full reperfusion] enhances NOS function in cardiac myocytes, 2) which specific NOS isoform is responsible for the enhanced NOS function in myocytes, and 3) to localize iNOS expression during SWOP. To address these questions, 10 dogs were instrumented to measure aortic and left ventricular pressures and wall thickness. At 1-2 wk after recovery, myocardial ischemia was induced regionally by a 10-min left circumflex CAO. After 24-h reperfusion, cardiac myocytes were isolated from the previously ischemic and nonischemic regions (n ϭ 6). Myocyte contractile function was assessed using a video motion detector at 1 Hz (35 Ϯ 2°C). At baseline, myocyte contractile function (% contraction) was similar in the two regions (ischemic 7.8 Ϯ 0.5% vs. nonischemic 7.8 Ϯ 0.2%). L-Arginine (1 mM) significantly reduced (P Ͻ 0.05) myocyte contraction in the ischemic (Ϫ34 Ϯ 3%, P Ͻ 0.05) but not (Ϫ7 Ϯ 4%) nonischemic regions; these responses were abolished by N G -nitro-L-arginine (1 mM), a nonspecific NOS inhibitor, as well as 2-amino-5,6-dihydro-6-methy-4H-1,3,thiazine (1 mM), a specific iNOS inhibitor. Immunohistochemistry also revealed enhanced iNOS expression in the myocardium and in particular the interstitial spaces in the ischemic zone. These results indicate that a brief ischemic episode upregulates iNOS function in myocytes as well as in the interstitial space between blood vessels and myocytes, strategically where it can regulate both vascular and myocyte function during the SWOP. preconditioning; nitric oxide; contraction; second window of protection ISCHEMIC PRECONDITIONING INVOLVES a brief ischemic episode, which increases the tolerance of the heart to subsequent myocardial ischemia (14,21,24). In addition, the late or delayed phase of preconditioning also referred to as the "second window of protection" (SWOP) induces cardioprotection 12-24 h after the initial ischemic stimulus. The protection conferred by the SWOP is sustained longer (3-4 days) than the early phase of preconditioning (2-3 h) in both myocytes and coronary vessels (17,20,22,27,28) and is modified by several pathways including nitric oxide (NO) (2,6,7,13,29,34). However, it remains unclear whether upregulation of NO synthase (NOS) during the SWOP alters myocyte contractile function and which specific isoform is responsible for the enhanced NOS function in cardiac myocytes. In the present study, we induced a brief episode (10 min) of regional myocardial ischemia in the canine model, where the heart is large enough that NO regulation of myocyte contractile function and localization of NOS ...

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Section: Discussionmentioning

confidence: 99%

Enhanced iNOS function in myocytes one day after brief ischemic episode

Kim¹,

Kim²,

Takagi³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…MITU is a completely different chemical entity from AMG; however, both demonstrated similar effects in aged WT mice but did not affect aged iNOS-KO-mouse hemodynamic function. Using bolus administration in the infarct model, Wildhirt demonstrates a specific linear relationship between AMG accumulations in tissues where elevated iNOS activity existed (Wildhirt et al, 1999). Both i.v.…”

Section: Inos Inhibition or Catecholamine Effectsmentioning

confidence: 99%

Modulation of iNOS activity in age-related cardiac dysfunction

2004

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“…In an experimental study, the authors reported that cardiac dysfunction development was accompanied by an increased myocardial iNOS activity. These authors suggested that aminoguanidine signifi cantly decreased iNOS activity and improved left ventricular performance in myocardial stunning (29). In our study, it was determined that AG and MP treatment signifi cantly decreased iNOS expression relative to CONT group.…”

Section: Discussionmentioning

confidence: 48%

Cardioprotective effect of aminoguanidine in combination with steroid therapy after blunt chest trauma

L¹,

Güzel²,

Hu³

et al. 2014

BLL

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Abstract:Background: Cardiac contusion is an important cause of mortality after blunt chest trauma (BCT). The aim of this study was to investigate the therapeutic effi cacy of the usage of aminoguanidine (AG), in myocardial damage occurring after BCT, alone and in combination with methylprednisolone (MP). Methods: Thirty-fi ve female Wistar albino rats were randomly assigned to fi ve groups (n = 7) including: sham controls (S); only cardiac contusion (CONT); cardiac contusion treated with methylprednisolone (CONT+MP); cardiac contusion treated with aminoguanidine (CONT+AG); and cardiac contusion treated with methylprednisolone and aminoguanidine (CONT+MP+AG). Seven days following the treatments, heart and serum specimens were evaluated histopathologically, immunohistochemically, and biochemically in all groups. Results: Serum AOPP and Tn-I levels increased signifi cantly after cardiac contusions. Haemorrhage, tissue degeneration, and necrosis development was evident following contusions. Increased iNOS expression in myocardial tissue was signifi cantly decreased in the CONT+AG+MP group compared to CONT+AG and CONT+MP groups (p = 0.001 and p = 0.011, respectively). The combined treatment of AG and MP increased Bcl-2 expression signifi cantly after contusions compared to the other treatment groups. Conclusions: Combined usage of AG, a selective iNOS inhibitor, with MP, in cardiac contusions, showed a more powerful cardioprotective effect by increasing Bcl-2 expression and reducing iNOS expression (Tab. 3, Fig. 4, Ref. 33). Text in PDF www.elis.sk.

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Aminoguanidine Inhibits Inducible NOS and Reverses Cardiac Dysfunction Late After Ischemia and Reperfusion - Implications for iNOS-Mediated Myocardial Stunning

Cited by 23 publications

References 27 publications

Enhanced iNOS function in myocytes one day after brief ischemic episode

Enhanced iNOS function in myocytes one day after brief ischemic episode

Modulation of iNOS activity in age-related cardiac dysfunction

Cardioprotective effect of aminoguanidine in combination with steroid therapy after blunt chest trauma

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