Sarcolemmal K
            <sub>ATP</sub>
            Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat

Patel, Hemal H.; Hsu, Anna; Peart, Jason Nigel John; Gross, Garrett J.

doi:10.1161/01.res.0000029085.69891.f2

Cited by 41 publications

(38 citation statements)

References 27 publications

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“…Furthermore, opioids have primarily been used for immediate protection. Only one group has previously shown a delayed protection by this stimulus, which was in rats (Patel et al 2002).…”

Section: Discussionmentioning

confidence: 98%

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

et al. 2005

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SummaryWe hypothesized that intraperitoneal injections of anaesthetics or fluid per se might evoke a delayed preconditioning-like response in mice hearts isolated and Langendorff perfused 24 h later. To test this, mice were given opioid anaesthesia by intraperitoneal injections or sham treated and the hearts were harvested and subjected to global ischaemia and reperfusion 24 h later in series 1. In series 2, mice were subjected to intraperitoneal injection of Ringer, sham needle prick procedure, or no intervention 24 h before heart isolation. In series 3, intraperitoneal Ringer injection 24 h earlier was compared with the effects of classic preconditioning or no pretreatment of the isolated heart or no treatment. Heart function was measured in all series. At the end of reperfusion, hearts in series 1 and 2 were frozen and infarct size was estimated by triphenyltetrazolium chloride solution. In series 3, separate hearts were frozen for immunoblotting to detect phosphorylation of mitogen-activated protein (MAP) kinases. Cardiac activation of nuclear factor kappa B (NFkB) was measured using a NFkB luciferase firefly reporter mouse.The ischaemia-induced impairment of left ventricular function was attenuated by opioid anaesthesia injected 24 h earlier, which also reduced infarct size. Injection of fluid, but not the sham needle prick procedure, reduced infarct size. The functional protection afforded by classic preconditioning and Ringer pretreatment was comparable. Neither cardiac MAP kinases nor NFkB were influenced by the interventions. In conclusion, this study demonstrates a delayed preconditioning-like effect of the heart caused by intraperitoneal administration of opioid anaesthetics and of fluid only in the mouse. The mechanism of protection remains to be determined.

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“…Furthermore, opioids have primarily been used for immediate protection. Only one group has previously shown a delayed protection by this stimulus, which was in rats (Patel et al 2002).…”

Section: Discussionmentioning

confidence: 98%

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

et al. 2005

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“…Morphine has been reported to protect against ischemiareperfusion injury and reduce myocardial infarct size in rats (Patel et al, 2002), as well as rabbits (Miki et al, 1998), and protect the cardiomyocytes in the chicken embryo (Liang and Gross, 1999). It has been further demonstrated that the ␦-receptor agonist DADLE and the -receptor agonist U-50488H could reduce myocardial infarct size and the incidence of arrhythmia in a cardiac ischemia-reperfusion model of the rat (Valtchanova-Matchouganska and Ojewole, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of opioid receptors has been shown to be cardioprotective by mimicking the effects of ischemic preconditioning in several experimental settings (Liang and Gross, 1999;Miki et al, 1998;Patel et al, 2002). In isolated rabbit hearts perfused on a Langendorff apparatus, morphine mimicked the effect of ischemic preconditioning in protecting the heart from being injured (Miki et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Yao

Wang

Cai

et al. 2007

Journal of Cell Science

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Survivin is known to be essential for cell division and to inhibit apoptosis during embryonic development and in adult cancerous tissues. However, the cardiovascular role of survivin is unknown. We observed that in cardiomyocytes cultured under conditions of serum and glucose deprivation (DEPV), the levels of survivin, Bcl-2 and extracellular signal-regulated kinase (ERK) were positively correlated with the anti-apoptotic action of a δ-opioid receptor agonist, [D-Ala2, D-Leu5]-enkephalin acetate (DADLE). By contrast, Bax translocation, mitochondrial membrane damage and reactive oxygen species (ROS) production were inversely correlated with the changes of survivin and Bcl-2. The use of RNA interference (RNAi) targeting survivin increased DEPV-induced cardiomyocyte apoptosis, whereas the anti-apoptotic effect of DADLE was blunted by survivin RNAi. Moreover, survivin transfection and overexpression provided protection against DEPV-induced cardiomyocyte apoptosis. Inhibition of ERK prevented the DADLE-induced decrease in apoptosis and Bax translocation, and increase in survivin and Bcl-2. DADLE-induced increase in survivin was also blunted by phosphoinositol 3-kinase (PI 3-kinase) inhibition. In conclusion, the present study provides the first direct evidence of an anti-apoptotic role of survivin mediating the anti-apoptotic effect of δ-opioid receptor activation in cardiomyocytes. ERK and PI 3-kinase were found to be upstream regulators of survivin. Mitochondrial membranes as well as ROS, Bcl-2 and Bax were also involved in this anti-apoptotic action.

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“…It is also noteworthy that in nonpreconditioned hearts from both male (21,27) and female (2) rats, it has been demonstrated that the putative mitochondrial K ATP channel antagonist 5-hydroxydecanoate (5-HD) has no effect on infarct size, suggesting that mitochondrial K ATP channels do not play a central role in the sexdependent differences in the susceptibility of the heart to myocardial infarction. This also indicates that the intrinsic, sex-dependent resistance of the heart to I/R injury is not analogous to a broad array of acquired cardioprotection models, almost all of which have been shown to be 5-HD sensitive (5,8,9,14,(21)(22)(23). One notable exception is cardioprotection acquired by long-term exercise, which has recently been shown to be HMR-1098 sensitive and 5-HD insensitive (2); interestingly, this study was conducted on female rats.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in myocardial infarct size are abolished by sarcolemmal K_ATPchannel blockade in rat

Johnson

Moore²,

Brown³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Sex differences in myocardial infarct size are abolished by sarcolemmal KATP channel blockade in rat. Am J Physiol Heart Circ Physiol 290: H2644 -H2647, 2006. First published February 10, 2006 doi:10.1152/ajpheart.01291.2005.-This study was conducted to examine the relationship between myocardial ATP-sensitive potassium (KATP) channels and sex differences in myocardial infarct size after in vitro ischemia-reperfusion (I/R). Hearts from adult male and female Sprague-Dawley rats were excised and exposed to an I/R protocol (1 h of ischemia, followed by 2 h of reperfusion) on a modified Langendorff apparatus. Hearts from female rats showed significantly smaller infarct sizes than hearts from males (23 Ϯ 4 vs. 40 Ϯ 5% of the zone at risk, respectively; P Ͻ 0.05). Administration of HMR-1098, a sarcolemmal K ATP channel blocker, abolished the sex difference in infarct size (42 Ϯ 4 vs. 45 Ϯ 5% of the zone at risk in hearts from female and male rats, respectively; P ϭ not significant). Further experiments showed that blocking the KATP channels in ischemia, and not reperfusion, was sufficient to increase infarct size in female rats. These data demonstrate that sarcolemmal KATP channels are centrally involved in mechanisms that underlie sex differences in the susceptibility of the intact heart to I/R injury. heart; ischemia; reperfusion ISCHEMIC HEART DISEASE is the leading cause of death in both males and females in the industrialized world, with myocardial infarction being the most common manifestation of ischemic heart disease (18). Among humans, premenopausal women have a lower risk of cardiovascular disease than age-matched men, and there is growing evidence that there is a sex-specific difference in the susceptibility of the myocardium to infarction after ischemia in dogs (15), rats (1, 4), mice (10, 11), as well as in humans (19).The cellular basis for sex differences in the susceptibility of the heart to ischemia-reperfusion (I/R) injury has not been elucidated. However, there has been speculation that that sarcolemmal ATP-sensitive potassium (sarcK ATP ) channels are involved. This speculation derives from observations that, relative to males, the protein expression of sarcK ATP channel subunits [inwardly rectifying K ϩ (Kir)6.2 and sulfonylurea receptor (SUR)2a] is greater in hearts from females (4, 26). Additionally, treatment of heart-derived H9c2 cells with 17␤-estradiol elicits a marked increase in the expression of both Kir6.2 and SUR2a subunits and an increase in the resistance of those cells to hypoxia-induced Ca 2ϩ overload that, in turn, could be abolished by sarcK ATP channel blockade with HMR-1098 (25). Whereas these observations clearly implicate a role for sarcK ATP channels in the sex-dependent differences in the susceptibility of the heart to I/R injury, pharmacological blockade of sarcK ATP channels in the intact heart has not been performed to confirm their role in sex-dependent cardioprotection. Thus the major objective of this study was to determine whether blocking sarcK ATP channels would ab...

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Sarcolemmal K _ATP Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat

Cited by 41 publications

References 27 publications

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Sex differences in myocardial infarct size are abolished by sarcolemmal K_ATPchannel blockade in rat

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Sarcolemmal K ATP Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat

Cited by 41 publications

References 27 publications

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

Intraperitoneal injection induces a delayed preconditioning-like effect in mice

Survivin mediates the anti-apoptotic effect of δ-opioid receptor stimulation in cardiomyocytes

Sex differences in myocardial infarct size are abolished by sarcolemmal KATPchannel blockade in rat

Contact Info

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Sarcolemmal K _ATP Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat

Sex differences in myocardial infarct size are abolished by sarcolemmal K_ATPchannel blockade in rat