Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts

Tatsumi, Tomohide; Akashi, Kazuko; Keira, Natsuya; Matoba, Satoaki; Mano, Akiko; Shiraishi, Jun; Yamanaka, Satoshi; Kobara, Miyuki; Hibino, Nobuhiro; Hosokawa, Satoru; Asayama, Jun; Fushiki, Shinji; Fliss, Henry; Nakagawa, Masao; Matsubara, Hiroaki

doi:10.1016/j.yjmcc.2004.06.014

Cited by 45 publications

(43 citation statements)

References 38 publications

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“…In this experiments, electron-lucent matrix, distorted cristae and variable swelling were found in the rat heart (Suliman et al 2004). Also, in the rats experiments, Tatsumi et al (Tatsumi et al 2004) has the similar findings. Compare to the sham group, there was less electron density in the mitochondria of septic hearts (Watts et al 2004).…”

Section: The Micro-characterization Of Septic Heart Tissuesupporting

confidence: 81%

Ulinastatin and Septic Cardiac Dysfunction

Lin¹,

Lin²

2012

The Transmission Electron Microscope

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Section: The Micro-characterization Of Septic Heart Tissuesupporting

confidence: 81%

Ulinastatin and Septic Cardiac Dysfunction

Lin¹,

Lin²

2012

The Transmission Electron Microscope

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“…LPS, TNF-α and IL-1β have direct negative inotropic effects on cardiomyocytes via induction of NO synthase. And over-production of NO causes contractile malfunction via cyclic guanosine 3', 5'-monophosphate in sepsis [8,32,33]. Moreover, phosphorylation of IκB has been shown to lead to the expression of NF-κB-controlled genes for cytokines that are associated with cardiac malfunction in the adult mammalian heart [34].…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice

Zhang

Zhu

Wang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Cardiac malfunction is a common complication in sepsis and significantly increases the mortality of patients in septic shock. However, no studies have examined whether andrographolide (And) reduces LPS-induced myocardial malfunction. Methods: Left ventricular systolic and diastolic functions were examined using echocardiography. TNF-a and IL-1ß protein levels were detected by an enzyme-linked immunosorbent assay (ELISA). NO oxidation products were determined using Griess reagent. Protein expression levels of inhibitors of NF-κBa (IκB) and phospho-IκB were determined via Western blot. Oxidative injury was determined by measuring myocardial lipid peroxidation and superoxide dismutase activity. Cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) and cardiac caspase 3/7 activity. Results: And blunted LPS-induced myocardial malfunctions in mice. LPS induced TNF-a, IL-1ß, and NO production as well as I-κB phosphorylation. Cardiac apoptosis was attenuated via incubation with And, but the extent of oxidative injury remained unaffected. Conclusion: And prevents LPS-induced cardiac malfunctions in mice by inhibiting TNF-a, IL-1ß, and NO production, IκB phosphorylation, and cardiac apoptosis, indicating that And may be a potential agent for preventing myocardial malfunction during sepsis.

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“…It is also likely that increased formation of reactive oxygen species, which also can occur in hyperglycemic conditions, can scavenge NO resulting in the formation of peroxynitrite and/or nitrotyrosine (NT). Peroxynitrite is a strong oxidant that can oxidize various biomolecules and can exert cytotoxic actions in cardiac and vascular tissue resulting in a state of cardiovascular depression (13,37,38).In the past, we have demonstrated that selective inhibition of iNOS in vitro in endothelium-denuded diabetic mesenteric arteries increases the potency of contractile responses to norepinephrine (1). This was recently confirmed by an in vivo study that reported increased pressor responses to norepinephrine on iNOS inhibition in acute diabetes (6).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

Nagareddy¹,

Xia²,

McNeill³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

138

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(MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N- [3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg iv) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction. inducible nitric oxide synthase; nitric oxide; cardiovascular abnormalities CHRONIC HYPERGLYCEMIA has been shown to directly affect the composition and structure of cardiac, vascular, and renal tissues, the progressive modification of which results in a deranged cardiovascular homeostasis (8). Cardiovascular depression, characterized by depressed mean arterial blood pressure (MABP), heart rate (HR), and attenuated pressor responses to vasoactive agents is one of the most notable manifestations of this derangement, particularly in animal models of Type 1 diabetes. Although the exact mechanisms by which diabetes contributes to cardiovascular depression are currently unknown, it is likely that hyperglycemia may initiate this abnormality through the activation of protein kinase C, increased activity of the polyol pathway, formation of nonenzymatic advanced glycosylation end products, oxidative stress, and/or possibly by induction of nitric oxide (NO) synthase (NOS) (19,42).The role of NO in the regulation of hemodynamics under hyperglycemic conditions has been controversial. Despite an impairment of endothelial function and reduced bioavailability of endothelium-derived NO, streptozotocin (STZ)-induced diabetic rats are not hypertensive but instead are normotensive or hypotensive (9,14,18,20,23,31,39,44). In addition, an increased dependence on a functional NO system at the onset of diabetes has been reported to prevent the development of hypertension in STZ diabetic rats (12). It has been suggested that increased NO synthesis m...

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Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts

Cited by 45 publications

References 38 publications

Ulinastatin and Septic Cardiac Dysfunction

Ulinastatin and Septic Cardiac Dysfunction

Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

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