Regulation of Prostaglandin Receptors in Myocardial Ischemia

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.

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

“…What then is the mechanism by which sulprostone causes the activation of KATP channels? Activation of Gq by EP1/EP3 (subgroups A and D) ultimately results, via phospholipase C (PLC)-mediated phosphoinositol (PI) hydrolysis, in the activation of protein kinase C (PKC; Hohlfeld, 1995;Katoh et al, 1995). The subsequent phosphorylation and opening of KATP channels by PKC leads to an increased potassium efflux, a shortening of the cardiac action potential and, hence, membrane hyperpolarization.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, EP, and EP3 are linked to multiple G-proteins (Gq and Gi/Gq respectively; see Trends Pharmacol. Sci., 1995) and activation of these receptors results in the hydrolysis of phosphatidylinositol (PI) and, hence, PKC activation (Hohlfeld, 1995;Katoh et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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

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Thiemermann

1996

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.

Effects of the prostanoid EP₃‐receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat

Zacharowski

Olbrich

Otto

et al. 1999

1 This study investigates the eects of two agonists of the prostanoid EP 3 -receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional myocardial ischaemia and reperfusion in the anaesthetized rat. 2 One hundred and sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg 71 , i.p.), ventilated (8 ± 10 ml kg 71 , 70 strokes min 71, inspiratory oxygen concentration: 30%; PEEP: 1 ± 2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3 M&B 28767 (0.5 mg kg 71 min 71 , i.v., n=7) or GR 63799X (3 mg kg 71 min 71 , i.v., n=7) caused signi®cant reductions in infarct size from 60+3% (25 min ischaemia and 2 h reperfusion; salinecontrol, n=8) to 39+6 and 38+4% of the area at risk, without causing a signi®cant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenuated the cardioprotective eects of both EP 3 -receptor agonists. The reduction in infarct size aorded by M&B 28767 was also abolished by glibenclamide and the protein kinase C (PKC) inhibitors staurosporine and chelerythrine. 4 Thus, M&B 28767 and GR 63799X reduce myocardial infarct size in the rat by a mechanism(s) which involves the activation of PKC and the opening of ATP-sensitive potassium channels.