Sustained anti-β-adrenergic effect of melatonin in guinea pig heart papillary muscle

Arvola, L.; Bertelsen, Eirin; Lochner, Amanda; Ytrehus, Kirsti

doi:10.1080/14017430500339347

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…3C). It also has beneficial short‐term effects on myocardial postischemic recovery, which have been attributed to its free radical scavenging, antioxidant [for reviews see 21,24], antiadrenergic [31, 71, 72] as well as receptor‐mediated actions [22]. However, the mechanism by which chronic melatonin treatment improves ischemia/reperfusion injury remains under investigation.…”

Section: Discussionmentioning

confidence: 99%

Chronic melatonin consumption prevents obesity‐related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet‐induced obesity

Nduhirabandi

Toit

Blackhurst

et al. 2010

Journal of Pineal Research

124

122

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Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of chronic melatonin administration on the development of the metabolic syndrome as well as ischemia-reperfusion injury in a rat model of diet-induced obesity (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4 mg/kg/day) was administered in the drinking water. After 16 wk, biometric and blood metabolic parameters were measured. Hearts were perfused ex vivo for the evaluation of myocardial function, infarct size (IFS) and biochemical changes [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4 expression). The high-calorie diet caused increases in body weight (BW), visceral adiposity, serum insulin and triglycerides (TRIG), with no change in glucose levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG, serum insulin, homeostatic model assessment index and thiobarbituric acid reactive substances in the DIO group. Melatonin reduced IFS in DIO and control groups and increased percentage recovery of functional performance of DIO hearts. During reperfusion, hearts from melatonin-treated rats had increased activation of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment prevented the metabolic abnormalities induced by DIO and protected the heart against ischemia-reperfusion injury. These beneficial effects were associated with activation of the reperfusion injury salvage kinases pathway.

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Section: Discussionmentioning

confidence: 99%

Chronic melatonin consumption prevents obesity‐related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet‐induced obesity

Nduhirabandi

Toit

Blackhurst

et al. 2010

Journal of Pineal Research

124

122

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“…PKC, on the other hand, although involved in the anti‐adrenergic actions of melatonin (Table 5), had no effect on the melatonin‐induced reduction in infarct size as inhibition of its activation, had no effect on the melatonin‐induced reduction in infarct size. Similarly, an important role for PKC in the sustained anti‐β‐adrenergic effects of melatonin in papillary muscle contractility could not be shown [18].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies using chick retinal neurons indicated that melatonin inhibited forskolin-and dopamine-stimulated cAMP accumulation via its receptor and an inhibitory G-protein [16,17]. Evidence has also been presented for the anti-adrenergic actions of melatonin in the heart, based on its effects on contractility of isolated papillary muscles [18,19]. It was also shown that the EC50 for isoproterenol in papillary muscle was increased approximately 10-fold by melatonin [19].…”

Section: Introductionmentioning

confidence: 99%

Melatonin receptor‐mediated protection against myocardial ischaemia/reperfusion injury: role of its anti‐adrenergic actions

Genade

Genis

Ytrehus

et al. 2008

Journal of Pineal Research

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Melatonin has potent cardioprotective properties. These actions have been attributed to its free radical scavenging and anti-oxidant actions, but may also be receptor mediated. Melatonin also exerts powerful anti-adrenergic actions based on its effects on contractility of isolated papillary muscles. The aims of this study were to determine whether melatonin also has anti-adrenergic effects on the isolated perfused rat heart, to determine the mechanism thereof and to establish whether these actions contribute to protection of the heart during ischaemia/reperfusion. The results showed that melatonin (50 microM) caused a significant reduction in both isoproterenol (10(-7) M) and forskolin (10(-6) M) induced cAMP production and that both these responses were melatonin receptor dependent, since the blocker, luzindole (5 x 10(-6) M) abolished this effect. Nitric oxide (NO), as well as guanylyl cyclase are involved, as L-NAME (50 microM), an NO synthase inhibitor and ODQ (20 microM), a guanylyl cyclase inhibitor, significantly counteracted the effects of melatonin. Protein kinase C (PKC), as indicated by the use of the inhibitor bisindolylmaleimide (50 microM), also play a role in melatonin's anti-adrenergic actions. These actions of melatonin are involved in its cardioprotection: simultaneous administration of L-NAME or ODQ with melatonin, before and after 35 min regional ischaemia, completely abolished its cardioprotection. PKC, on the other hand, had no effect on the melatonin-induced reduction in infarct size. Cardioprotection by melatonin was associated with a significant activation of PKB/Akt and attenuated activation of the pro-apoptotic kinase, p38MAPK during early reperfusion. In summary, the results show that melatonin-induced cardioprotection may be receptor dependent, and that its anti-adrenergic actions, mediated by NOS and guanylyl cyclase activation, are important contributors.

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“…Furthermore, the beneficial effects of exogenous melatonin on the heart in physiological conditions such as ageing as well as in pathophysiological conditions, for example hyperthyroidism (Ghosh et al 2007), cadmium-induced oxidative damage (Mukherjee et al 2011) and myocardial hypertrophy (Reiter et al 2010c) have been demonstrated. Besides its direct free radical scavenger and indirect antioxidant activity (Tengattini et al 2008), the contribution of MT receptors in the cardioprotective properties has also been emphasized (Arvola et al 2006, Sallinen et al 2007, Genade et al 2008, Grossini et al 2011, Lamont et al 2011. Besides its direct free radical scavenger and indirect antioxidant activity (Tengattini et al 2008), the contribution of MT receptors in the cardioprotective properties has also been emphasized (Arvola et al 2006, Sallinen et al 2007, Genade et al 2008, Grossini et al 2011, Lamont et al 2011.…”

Section: Cardiovascular Effects Of Melatoninmentioning

confidence: 99%

“…However, the mechanism of the actions of melatonin is still complex and not yet fully explored. Besides its direct free radical scavenger and indirect antioxidant activity (Tengattini et al 2008), the contribution of MT receptors in the cardioprotective properties has also been emphasized (Arvola et al 2006, Sallinen et al 2007, Genade et al 2008, Grossini et al 2011, Lamont et al 2011. Melatonin supplementation has largely been considered as a potential pharmacological agent in non-dipper and individuals with hypertension (Paulis & Simko 2007, Grossman et al 2011, Kozirog et al 2011.…”

Section: Cardiovascular Effects Of Melatoninmentioning

confidence: 99%

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

2012

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The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.

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Sustained anti-β-adrenergic effect of melatonin in guinea pig heart papillary muscle

Abstract: Receptor-mediated immediate and sustained anti-ss-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified.

Cited by 5 publications

References 21 publications

Chronic melatonin consumption prevents obesity‐related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet‐induced obesity

Chronic melatonin consumption prevents obesity‐related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet‐induced obesity

Melatonin receptor‐mediated protection against myocardial ischaemia/reperfusion injury: role of its anti‐adrenergic actions

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

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