Postconditioning Improves Postischemic Cardiac Dysfunction Independently of Norepinephrine Overflow After Reperfusion in Rat Hearts: Comparison With Preconditioning

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

doi:10.1097/fjc.0b013e3181bfb1c1

Cited by 11 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The K ATP channels reduced the concentration of intracellular Ca 2+ , which contributed to maintain the plateau period of the action potential. Thus, deficient K ATP channels confer a greater susceptibility to calcium overload in A/R, impairing the contractile recovery under various conditions of high metabolic demand (Tawa et al, 2010). These changes were more pronounced in the pinacidil groups.…”

Section: +mentioning

confidence: 84%

Effect of pinacidil on rat ventricular myocytes during transient hypoxia and reperfusion

Dong

Zhu

2014

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of this study was to evaluate the cardioprotective effect of pinacidil postconditioning on rat hearts with transient hypoxia and reperfusion. An acute myocardial anoxia-reperfusion rat model was created by ligating coronary arteries for 10 min and subsequent reperfusion for 60 min. Twenty-four rats in 4 groups received different treatments: normal hearts as control (N = 6), anoxia-reperfusion (A/R) only (N = 6), pinacidil postconditioning (N = 6), and pinacidil plus adenosine triphosphate-sensitive potassium channel inhibitors (glibenclamide) (N = 6). The kinetic parameters and electrophysiological properties, including early apoptosis protein expression changes of Bax, Bcl-2, and FN were examined using the isolated perfusion and patch-clamp technique and immunohistochemistry. The left ventricular systolic pressure and maximum -dp/dt in A/R groups were significantly higher than those in the control group (P < 0.05). The left ventricular developing pressure, maximum +dp/dt, and heart rate in the A/R group were slightly decreased. The pinacidil-postconditioned group has better cardiac function recovery after ischemia/reperfusion than the A/R group (P < 0.01). In addition, using the patch-clamp technique, the mean open time and conductance values are significantly higher in the pinacidil postconditioning group, compared with those in the A/R group. The FN) increased during A/R, while Bcl-2 protein expression decreased. A significant difference was found in the pinacidil treatment group relative to the A/R group. Pinacidil postconditioning can exert cardioprotective effects on A/R-injured rat hearts, which may indicate a potential application of pinacidil postconditioning to protect A/R-injured hearts.

show abstract

Section: +mentioning

confidence: 84%

Effect of pinacidil on rat ventricular myocytes during transient hypoxia and reperfusion

Dong

Zhu

2014

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Indeed, we have shown the inhibitory effect of NO on NE overflow and deterioration of cardiac function after ischemia/reperfusion in isolated rat hearts. 12 Considering these findings, therefore, ET B receptor stimulation by ET-1 generated from exogenously applied big ET-1 induces the increase in NO production, which is responsible for suppression of NE overflow and improvement of cardiac dysfunction after ischemia/reperfusion. However, beneficial effect of exogenously applied big ET-1 especially on systolic disorder slightly remained in the presence of NOARG even though this inhibitor completely inhibited the increase in NO production by it, suggesting a possible involvement of mediator other than NO in the big ET-1-induced action.…”

Section: Discussionmentioning

confidence: 96%

“…12 Norepinephrine Assay NE in the coronary effluent was measured with highperformance liquid chromatography and an amperometric detector (ECD-100, Eicom, Kyoto, Japan), as reported previously. 12…”

Section: Experimental Protocolmentioning

confidence: 99%

See 1 more Smart Citation

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

Tawa

Fukumoto²,

Ohkita³

et al. 2011

Journal of Cardiovascular Pharmacology

Self Cite

View full text Add to dashboard Cite

We have recently shown that an appropriate amount of exogenous big endothelin-1 (ET-1) has beneficial effects on ischemia-/reperfusion-induced norepinephrine overflow and cardiac dysfunction in rat hearts and that these effects occur through a conversion to ET-1 by endothelin-converting enzyme and following stimulation of ETB receptor. In this study, we examined the possible involvement of nitric oxide (NO) in the big ET-1-induced cardioprotective effects. According to the Langendorff technique, isolated rat hearts were subjected to 40-minute global ischemia followed by 30-minute reperfusion. Exogenous big ET-1 (0.3 nM) significantly increased NOx (NO2/NO3) level in the coronary effluent after onset of reperfusion. This effect was markedly attenuated by treatment with SM-19712 (selective endothelin-converting enzyme inhibitor), A-192621 (selective ETB receptor antagonist), or NG-nitro-l-arginine (nonselective NO synthase inhibitor), respectively. In addition, N-nitro-l-arginine blunted big ET-1-induced suppression of norepinephrine overflow and improvement of cardiac dysfunction after ischemia/reperfusion. These findings suggest that NO produced by ETB receptor activation plays an important role in exogenous big ET-1-induced actions.

show abstract

“…In addition, we have recently reported that nitric oxide has an inhibitory effect on NE overflow after cardiac ischemia/reperfusion. 27 Therefore, we presume whether nitric oxide acts as the downstream mediator of ET B receptor activation by ET-1 generated from exogenously applied big ET-1 via ECE. It has been mentioned that ET-1 plays a critical role in heart injury mostly through the activation of ET A receptors.…”

Section: Discussionmentioning

confidence: 99%

Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts

et al. 2010

Self Cite

View full text Add to dashboard Cite

Endothelin-1 (ET-1) is involved in norepinephrine (NE) overflow and cardiac dysfunction after myocardial ischemia/reperfusion via the activation of ET A receptors. As ET-1 is generated from big ET-1 via endothelin-converting enzyme (ECE), ischemia/ reperfusion-induced cardiac injury may be exacerbated by exogenous big ET-1. The aim of this study was to investigate the influence of exogenously applied big ET-1 on ischemia/reperfusion-induced NE overflow and cardiac dysfunction. According to the Langendorff technique, isolated rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. Exogenous big ET-1 (0.1, 0.3 and 1 nM) was perfused, beginning 15 min before ischemia. Unexpectedly, higher doses (0.3 and 1 nM) of big ET-1 significantly improved indices of left ventricular function after ischemia/reperfusion, such as left ventricular developed pressure (LVDP), the maximum value of the first derivative of left ventricular pressure (dP/dt max ) and left ventricular end diastolic pressure (LVEDP). In addition, big ET-1 significantly suppressed excessive NE overflow in the coronary effluent from the postischemic heart. These effects of big ET-1 were markedly attenuated by treatment with SM-19712 (selective ECE inhibitor) or A-192621 (selective ET B receptor antagonist). On the other hand, those were not potentiated even though combined with ABT-627 (selective ET A receptor antagonist). From these findings, we suggest that exogenous big ET-1 has beneficial effects on ischemia/reperfusion-induced cardiac injury. It seems likely that big ET-1 is converted to ET-1, locally in the heart, and this ET-1 preferentially binds to ET B receptors to exert its related beneficial actions. Keywords: big endothelin-1; endothelin-1; ischemia/reperfusion; norepinephrine INTRODUCTION Endothelin-1 (ET-1) was originally found as a 21-amino-acid vasoconstrictor peptide produced by vascular endothelial cells. 1 This peptide is most abundant in the cardiovascular system, and at least two distinct ET receptors, ET A and ET B , have been identified. ET A receptors mediate vasoconstriction and cell proliferation, whereas ET B receptors are important for the clearance of ET-1, endothelial cell survival, the release of nitric oxide and prostacyclin. 2 There is accumulating evidence that ET-1 is closely related to the pathogenesis and development of several cardiovascular diseases. 3,4 It has been demonstrated that ischemia increases ET-1-binding sites in cardiac membranes. 5 In addition, we have recently noted that left ventricular ET-1 content is increased by ischemia/reperfusion in isolated rat hearts, and postischemic cardiac dysfunction is improved by suppressing the ET-1 biosynthesis. 6 These findings imply that endogenously generated ET-1 plays an important role in the pathophysiology of myocardial ischemia/reperfusion. Indeed, both selective

show abstract

Postconditioning Improves Postischemic Cardiac Dysfunction Independently of Norepinephrine Overflow After Reperfusion in Rat Hearts: Comparison With Preconditioning

Cited by 11 publications

References 35 publications

Effect of pinacidil on rat ventricular myocytes during transient hypoxia and reperfusion

Effect of pinacidil on rat ventricular myocytes during transient hypoxia and reperfusion

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

Effects of exogenous big endothelin-1 on postischemic cardiac dysfunction and norepinephrine overflow in rat hearts

Contact Info

Product

Resources

About