Cardioprotective Effects of Nicorandil

Gross, Garrett J.; Auchampach, John A.; Maruyama, Masahiko; Warltier, David C.; Pieper, Galen M.

doi:10.1097/00005344-199206203-00006

Cited by 76 publications

(33 citation statements)

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“…There is now good evidence that the potent cardioprotective effects caused by 'ischaemic preconditioning' of the myocardium are also due to activation of KATP channels, as (i) the cardioprotective effects of ischaemic preconditioning are abolished by the KATP channel inhibitors, glibenclamide or 5-HD Toombs et al, 1993;Walsh et al, 1994;Hide & Thiemermann, 1996) and (ii) intracoronary administration of KATP channel openers (aprikalim, nicorandil, cromakalim, pinacidil), at doses which do not cause a significant fall in blood pressure, produce a marked reduction in infarct size (Auchampach et al, 1991;Gross et al, 1992;Grover et al, 1990), which is of a similar magnitude to that seen with ischaemic preconditioning. Indeed, it has been proposed that the cardioprotective effects of ischaemic preconditioning are secondary to the release of endogenous mediators such as adenosine (Liu et al, 1991;Thornton et al, 1992) which, via the stimulation of G protein-coupled (Gq/Go) receptors and activation of PKC, ultimately leads to the long-lasting opening of KATP channels.…”

Section: Discussionmentioning

confidence: 99%

Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Hide

Thiemermann

1996

British J Pharmacology

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1 This study examined whether (i) a 1 h pretreatment with or (ii) a continuous infusion of sulprostone reduces myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min) in the anaesthetized rabbit. In addition, we investigated whether the observed cardioprotective effect of this selective agonist of prostanoid EP,/EP3 receptors were due to the activation of ATPsensitive potassium (KATP) channels.2 In anaesthetized rabbits pretreated with vehicle (5% ethanol in 0.9% saline; 0.05 ml min-', i.v.) infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 120 min of reperfusion was 59 + 4% (n = 10). Pretreatment of rabbits with sulprostone (1.0 ug kg-' min-' for 1 h, discontinued immediately prior to coronary artery occlusion) did not reduce infarct size (60 + 4%; n = 4). In contrast, a continuous infusion of sulprostone (1.0 ig kg-' min-') starting 10 min prior to the onset of LAL occlusion and continued throughout the experiment, significantly reduced infarct size (41 + 5%, n = 6) when compared to the respective vehicle-treated controls (57 + 4%, n = 10; P <0.05). Sulprostone (pretreatment or continuous infusion) had no effect on any of the haemodynamic parameters measured. 3 The reduction in infarct size afforded by continuous infusion of sulprostone was abolished by pretreatment of rabbits with the KATP channel blocker 5-hydroxydecanoate (5-HD 5 pg kg-'; 63+4%; n =6). When administered alone, 5-HD had no effect on infarct size when compared to control (52+6, n=10). 4 We propose that a continuous infusion of the selective EP,/EP3 prostanoid receptor agonist, sulprostone, reduces infarct size in the anaesthetized rabbit by a mechanism that involves the opening of KATP channels.

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Section: Discussionmentioning

confidence: 99%

Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Hide

Thiemermann

1996

British J Pharmacology

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“…There is now good evidence that the potent cardioprotective effects caused by 'ischaemic preconditioning' of the myocardium are also due to activation of KATP channels, as (i) the cardioprotective effects of ischaemic preconditioning are abolished by the KATP channel inhibitors, glibenclamide or 5-HD Toombs et al, 1993;Walsh et al, 1994), and (ii) intracoronary administration of KATP channel openers (aprikalim, nicorandil, cromakalim, pinacidil), at doses which do not cause a significant fall in blood pressure, produce a marked reduction in infarct size (Grover et al, 1990;Auchampach et al, 1991;Gross et al, 1992), which is of a similar magnitude to that seen with ischaemic preconditioning. Indeed, it has been proposed that the cardioprotective effects of ischaemic preconditioning are secondary to the release of endogenous adenosine, which in turn, activates the Al adenosine receptor Thornton et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Reduction by prostaglandin E₁ or prostaglandin E₀ of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

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Ney

Piper

et al. 1995

British J Pharmacology

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1 This study examined whether pretreatment of rabbits with infusions of prostaglandin El (PGEI) or prostaglandin Eo (PGEO) (which were terminated prior to the onset of ischaemia) reduce myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effects of these two prostaglandins were due to the activation of ATP-sensitive potassium (KATP) channels. 2 In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 59 + 4% (n = 10). PGEI or PGEo treatment (1.0 ,yg kg-' min-'), administered as 1 h pretreatments (0.05 ml min-', i.v.), significantly reduced infarct size to 44 + 6% (n = 6) or 42 + 1 % (n = 6), respectively. PGE, or PGEo pretreatment resulted in a significant reduction in mean arterial blood pressure, which returned to baseline within 15 min of discontinuation of the infusion (i.e. prior to LAL ligation). 3 The reduction in infarct size afforded by PGE, was abolished by pretreatment of rabbits with the KATP channel blockers, glibenclamide (60 + 4%; n =8) or 5-hydroxydecanoate (58 + 6%; n = 6). Similarly, glibenclamide also largely attenuated the reduction in infarct size afforded by PGEo (52 + 3%; n = 8).4 We propose that a 1 h pretreatment of PGEI or PGEO reduces infarct size by activating protein kinase C resulting in the opening of KATP channels.

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“…Bcl-2; cyclooxygenase-2; infarct size; ischemia-reperfusion NICORANDIL IS A HYBRID AGENT with ATP-sensitive K ϩ (K ATP ) channel opener-like and nitrate-like properties (40,61) and has been shown to have a protective effect in several experimental animal models of myocardial ischemia-reperfusion (1,15,16,21,24,30,31,36,37,45,46,57,69). Clinical studies (23,34,43,54,60) have shown that nicorandil attenuates ECG changes during coronary occlusion and that it improves the functional recovery of the reperfused myocardium in patients with acute myocardial infarction.…”

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confidence: 99%

Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits

Tang

Xuan

Zhu

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Nicorandil has been shown to induce an infarct-limiting effect similar to that induced by the early phase of ischemic preconditioning (PC). The goals of this study were to determine whether nicorandil induces a delayed cardioprotection that is analogous to the late phase of ischemic PC and, if so, whether nicorandil-induced late PC is associated with upregulation of cardioprotective proteins. Chronically instrumented, conscious rabbits received vehicle (intravenous normal saline; control group, n = 10), nicorandil (100 μg/kg bolus + 30 μg·kg–1·min–1 iv for 60 min; nicorandil group, n = 10), or ischemic PC (6 cycles of 4-min coronary occlusion/4-min reperfusion; PC group, n = 8). Twenty-four hours later, rabbits underwent a 30-min coronary occlusion, followed by 3 days of reperfusion. Myocardial infarct size was significantly reduced in rabbits pretreated with nicorandil (27.5 ± 5.3% of the risk region) or with ischemia (30.3 ± 4.2%) versus controls (59.1 ± 4.7%, P < 0.05 vs. both). Furthermore, the expression of cyclooxygenase-2 (COX-2) and Bcl-2 was significantly elevated (+38% and +126%, respectively; P < 0.05) in myocardium of rabbits given nicorandil 24 h earlier versus controls. We conclude that nicorandil induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by upregulating COX-2 and Bcl-2.

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Cardioprotective Effects of Nicorandil

Cited by 76 publications

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Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Reduction by prostaglandin E₁ or prostaglandin E₀ of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits

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Cardioprotective Effects of Nicorandil

Cited by 76 publications

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Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Sulprostone‐induced reduction of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels

Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits

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Reduction by prostaglandin E₁ or prostaglandin E₀ of myocardial infarct size in the rabbit by activation of ATP‐sensitive potassium channels