Contribution of Nitric Oxide in Big Endothelin-1–induced Cardioprotective Effects on Ischemia/Reperfusion Injury in Rat Hearts

Tawa, Masashi; Fukumoto, Taiki; Ohkita, Mamoru; Yamashita, Naoto; Geddawy, Ayman; Imamura, Teruhiko; Ayajiki, Kazuhide; Okamura, Tomio; Matsumura, Yasuo

doi:10.1097/fjc.0b013e31821325ad

Cited by 10 publications

(8 citation statements)

References 21 publications

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“…It is involved in many physiological and pathological processes. Low levels of iNOS expression have been proven to play an important role in protecting flaps from I/R injury [2,12,13].…”

Section: Introductionmentioning

confidence: 99%

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning

Yang

Angel

Pang

et al. 2012

HAND

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Background/Objective Preconditioning has been considered promising for the treatment of ischemic flaps. In this study, the therapeutic effect of postconditioning was compared with that of preconditioning during ischemia/reperfusion (I/R) injury, and a role of inducible nitric oxide synthase (iNOS) in postconditioning treatment was also explored. Methods Sixty rats were randomly divided into four groups with 15 rats in each group. Ischemic injury was induced in a rat's gracilis muscle flap model. Preconditioning and postconditioning were performed respectively on the flaps in the pre-con group and the post-con group. No treatment was given to the flaps in the control group, and flaps without I/R injury were used as a sham control. Muscle viability ratio, histology, and gene expression of iNOS were examined at different time intervals (3, 12, and 18 h). Results A significantly higher survival ratio was observed in both the pre-con group (78.98±3.39, 62.74±3.7, and 54.42 ± 4.45 %) and the post-con group (77.42 ± 4.14, 59.74±6.67, and 49.52±4.13 %) than the control group (45.22±3.69, 42.44±3.76, and 33.2±3.29 %) at 3, 12, and 18 h postoperatively (P<0.05). There was no statistical difference between the pre-con group and the post-con group (P>0.05). Histological examination showed delayed and attenuated tissue damage in both the pre-con group and the post-con group when compared to that of the control group. A higher expression of iNOS was observed in both the pre-con group and the post-con group than the control group and the sham group (P<0.05). Conclusions Significant improvement of flap survival could be achieved by both preconditioning and postconditioning treatments; however, better protection could be provided by preconditioning. The higher expression of iNOS may play an important role in the therapeutic effect of postconditioning during I/R injury.

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“…It is involved in many physiological and pathological processes. Low levels of iNOS expression have been proven to play an important role in protecting flaps from I/R injury [2,12,13].…”

Section: Introductionmentioning

confidence: 99%

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning

Yang

Angel

Pang

et al. 2012

HAND

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“…However, this may not be the case because the exogenous big ET-1-induced inhibitory effect on NE overflow after 40-min global ischemia/reperfusion was completely cancelled by treatment with the nitric oxide (NO) synthase (NOS) inhibitor N G -nitro-L-arginine (NOARG) [46]. This finding suggests the involvement of NO derived from NOS in ET B R-mediated inhibitory modulation of carrier-mediated NE release.…”

Section: Et-1 System In Ne Overflowmentioning

confidence: 99%

“…Briefly, big ET-1 at a concentration of 0.3 nM most efficiently improved left ventricular dysfunction after reperfusion. In addition, this beneficial effect of exogenously applied big ET-1 was canceled by respective treatment with SM-19712, A-192621, and NOARG [41, 46]. …”

Section: Et-1 System In Ne Overflowmentioning

confidence: 99%

Endothelin-1 and Norepinephrine Overflow from Cardiac Sympathetic Nerve Endings in Myocardial Ischemia

Tawa

Yamamoto

Ohkita

et al. 2012

Cardiology Research and Practice

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In protracted myocardial ischemia, sympathetic activation with carrier-mediated excessive norepinephrine (NE) release from its nerve endings due to reversal of NE transporter in an outward direction is a prominent cause of arrhythmias and cardiac dysfunction. Endothelin-1 (ET-1) and its receptors are intimately involved in the regulation of this carrier-mediated NE overflow in protracted myocardial ischemia. The ET-1 system is often complex, sometimes involving opposing actions depending on which receptor subtype is activated, which cells are affected, and whether stimuli are endogenously generated or exogenously applied. Therefore, a detailed understanding of the ET-1 system is important for applying drugs acting on this system in clinical settings for the treatment of ischemic cardiac disease. This article provides a detailed analysis of how the ET-1 system is involved in the regulation of carrier-mediated NE release from sympathetic nerve endings in protracted myocardial ischemia.

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“…Acupuncture, the most well-known complementary and alternative medical approach, has been applied to prevent and cure many diseases such as angina [6], palpitation [7], stroke [8], and disruption of the left cardiac function in coronary heart disease (CHD) [9] for more than 2000 years. Recent studies show that acupuncture treatment can improve regeneration capacity of local micro-vascular and collateral circulation during myocardia ischemia; thereby ameliorating ischemia symptoms [10-13]. It not only quickly relieves the symptoms of acute angina pectoris, but also improves nitroglycerine’s therapeutic effects [14].…”

Section: Introductionmentioning

confidence: 99%

A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris

Wang

Shen

Chen

et al. 2015

BMC Complement Altern Med

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BackgroundAngina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6). Furthermore, we employ high-throughput sequencing technology to investigate the gene expression profiling and determine involvement of histone modifications in the regulation of genes after electro-acupuncture treatment.Methods/DesignA randomized, controlled, double-blinded (assessor and patients) trial will be carried out. Sixty participants will be randomly assigned to two acupuncture treatment groups and one control group in a 1:1:1 ratio. Participants in acupuncture groups will receive 12 sessions of electro-acupuncture treatment across 4 weeks, followed by a 12-week randomization period. The acupuncture groups are divided into Neiguan (PC6) on Pericardium Meridian of Hand-jueyin or a non-acupoint. The primary clinical measure of effect is the frequency of angina attacks between these groups for four weeks after randomization. RNAs are extracted from peripheral neutrophils collected from all participants on day 0, day 30, and week 16, and are processed to RNA-Seq. We then investigate profiles of histone modifications by ChIP-Seq, for H3 Lysine 4 (H3K4me) and acetylation of H3 Lysine 27 (H3K27ac), in the presence or absence of acupuncture treatment.DiscussionThis study determines the efficacy and mechanisms of electro-acupuncture on stable angina pectoris. We focus on effectiveness of acupuncture on alleviating symptoms of myocardial ischemia and the gene regulation and the chromatin remodeling marks, including H3K4me1, H3K4me2, and H3K27ac, which could be key factors for regulating gene expressions caused by electro-acupuncture treatment at Neiguan. This is the first genome-wide study of electro-acupuncture treatment in angina patients, and will provide valuable information for future studies in the fields of acupuncture and its underlying mechanisms.Fourteen patients have been recruited since recruitment opened in November of 2012. This study is scheduled to end in November of 2014.Trials registrationChiCTR-TRC-12002668

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Contribution of Nitric Oxide in Big Endothelin-1–induced Cardioprotective Effects on Ischemia/Reperfusion Injury in Rat Hearts

Cited by 10 publications

References 21 publications

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning

Endothelin-1 and Norepinephrine Overflow from Cardiac Sympathetic Nerve Endings in Myocardial Ischemia

A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris

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