Beneficial Effects of Angiotensin I Converting Enzyme Inhibitor on Post-ischemic Contractile Function of Perfused Rat Heart

Tanonaka, Kouichi; Kamiyama, Toru; Takezono, Aya; Sakai, Kimiko; Takeo, Satoshi

doi:10.1006/jmcc.1996.0156

Cited by 13 publications

(9 citation statements)

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“…Consistent with this notion are the beneficial effects reported for angiotensin-converting enzyme (ACE) inhibitors administered either before 24 or during 25 cardiopulmonary bypass on various parameters of myocardial ischemic injury 24,25 and on contractile dysfunction and metabolic derangement induced by ischemia and reperfusion. 26 These may be mediated by the capacity of ACE inhibitors to prevent MAPK activation. 6 Additional larger-scale clinical trials are needed to establish more definitively the role of the MAPKs as potential molecular targets for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass

Talmor

Applebaum

Rudich

et al. 2000

Circulation Research

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Abstract-Mitogen-activated protein kinases (MAPKs) have been shown to be activated in both in vitro and in vivo models of cardiac tissue in response to ischemia/reperfusion injury. We investigated whether MAPKs are activated in human heart during coronary artery bypass grafting (CABG) surgery. During elective CABG surgery of 8 patients, 3 right atrial appendage biopsies were obtained at baseline, at the end of cross-clamping, and after coronary reperfusion. The expression of the p38-MAPK, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERK1/2) MAPKs was not altered during CABG. The phosphorylation and activation of both ERK1/2 and p38-MAPK were increased Ϸ2-fold by ischemia and even more (8-and 4-fold, respectively) by reperfusion. Although the ischemic period did not result in a significant activation of JNK, an Ϸ6-fold increase in JNK activity could be observed after reperfusion.In conclusion, distinct activation patterns of ERK1/2, p38, and JNK MAPKs can be observed in human heart during CABG. (Circ Res. 2000;86:1004-1007.)Key Words: myocardium Ⅲ ischemia/reperfusion Ⅲ stress-activated protein kinases T he mitogen-activated protein kinases (MAPKs) are activated by diverse stimuli and appear to mediate cellular responses including proliferation, differentiation, and adaptation to stress. 1,2 Three major subfamilies have been characterized, including the extracellular signal-regulated kinases (ERK1/2), the c-Jun N-terminal kinases (JNK1/2), and the p38-MAPKs. 2 It has been previously reported that although the ERKs are mainly involved in mediating anabolic processes such as cell division, growth, and differentiation, the JNKs and the p38-MAPKs are generally associated with cellular response to diverse stresses (reviewed in References 3 and 4).In recent years, the possible importance of MAPK activation in the heart during ischemia/anoxia and reoxygenation has been raised. 2,4 The JNKs and the p38-MAPKs have been consistently shown to be activated by myocardial ischemia/reperfusion in both animal models 4,5 and in cardiomyocyte cell lines. 6,7 The ERKs, however, have been shown to be activated in isolated animal hearts by ischemia/reperfusion by some, 5,8 although not all investigators, 4,9 possibly in response to oxidative stress. 9,10 The exact role of the MAPKs in cardiac pathophysiology in humans has not been fully elucidated, partly because of limited information regarding the activation pattern of the MAPKs in the human heart. A recent study demonstrated the expression of JNK, p38-MAPK, and ERK1/2 in the human heart. A potential clinical relevance for their action was demonstrated by an increased activity of JNK and p38-MAPK in heart failure secondary to ischemic heart disease. 11In the present study, we aimed at evaluating both the expression and activation of the different MAPKs in nonfailing human hearts by cardiopulmonary bypass during the course of coronary artery bypass grafting (CABG) surgery. Materials and MethodsThe study was performed on right atrial appendage samples ob...

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Section: Discussionmentioning

confidence: 99%

Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass

Talmor

Applebaum

Rudich

et al. 2000

Circulation Research

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“…The fibres obtained from control rats were used in this experiment, and the developed contractions were compared with those of the fibres without trandolaprilat treatment. The concentration of trandolaprilat used for this study was decided on the basis of the findings in a previous study from our laboratory that 30 to 100 μ m of this agent were capable of exerting cardioprotective effects in ischaemic/reperfused rat hearts (Tanonaka et al , 1996).…”

Section: Methodsmentioning

confidence: 99%

Effects of long‐term treatment with trandolapril on sarcoplasmic reticulum function of cardiac muscle in rats with chronic heart failure following myocardial infarction

Yamaguchi

Sanbe

Takeo

1998

British J Pharmacology

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1 Calcium transport activity of isolated cardiac sarcoplasmic reticulum (SR) including Ca 2+ uptake and release is decreased in animals with chronic heart failure (CHF) following myocardial infarction. The present study was undertaken to determine whether an angiotensin converting enzyme (ACE) inhibitor, trandolapril, improves cardiac sarcoplasmic reticular function in animals with CHF following myocardial infarction. 2 CHF was induced by left coronary artery ligation in rats, which resulted in an infarction of approximately 45% of the left ventricle. Aortic¯ow and cardiac output index were decreased, and left ventricular end-diastolic pressure was increased 8 weeks after the operation, suggesting the development of CHF. 3 The developed force transients of cardiac skinned ®bres of the rats with CHF were decreased when the skinned ®bre was preloaded for 0.25 ± 1 min with 10 75 M Ca 2+ (48 ± 88%) and when preloaded with 10 76 M Ca 2+ and then exposed to 0.1 ± 1 mM ca eine (45 ± 93%). 4 The [ 3 H]-ryanodine-binding activity in SR-enriched fractions was reduced by 23% in the CHF group. These results suggest that the amount of Ca 2+ released from SR is decreased due to a reduced rate of SR Ca 2+ uptake and a downregulation of the SR Ca 2+ -release channel. 5 Rats were treated orally with 3 mg kg 71 day 71 trandolapril from the 2nd to the 8th week after the coronary artery ligation. Treatment with trandolapril attenuated the reduction in aortic¯ow and cardiac output index and the increase in left ventricular end-diastolic pressure, and improved the developed force transients of the skinned ®bre of the animal with CHF without causing a reduction of infarct size. Treatment with trandolapril also attenuated the reduction in ryanodine receptor density in the viable left ventricle of the rat with CHF. 6 It is concluded that long-term treatment with trandolapril attenuates cardiac SR dysfunction in rats with CHF and that the mechanism underlying this e ect is, at least in part, attributed to prevention of downregulation of Ca 2+ release channel.

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“…Delapril at 30 mg/kg/day was also reported to inhibit the progression of renal damage in SHR, whereas hydralazine having the same antihypertensive effect did not protect renal function.l'In an oral toxicity study of delapril in rats, the no effective dose level was reported to be 100 mg/kg/day.' 8 In this study, we administered 30 mg/kg/day (lowdose) and 90 mg/kg/day (high-dose) of delapril orally for 7 days.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effect of orally administered angiotensin-converting enzyme inhibitor against ischemia

Hara

Iguchi

et al. 1999

Jpn J Thorac Caridovasc Surg

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Angiotensin-converting enzyme inhibitors are reported to be cardioprotective against ischemia/reperfusion injury. Few studies have been made, however, on the cardioprotectiveness of orally administered angiotensin-conrerting enzyne inhibitors. Wistar rats were pretreated with oral delapril--30 mg/kg/day in the low-dose group and 90 mg/kg/day in the high-dose group--for one week. Cardiac function recovery was assessed after ischemia/reperfusion in the isolated working heart model. Rat hearts in the high-dose group were also reperfused with a solution containing nitro-L-arginine methyl ester, a nitric-oxide synthase inhibitor. Oral pretreatment of delapril did not affect baseline cardiac function. The percentage of cardiac output recovery for controls was 22 +/- 4.5%, for the low-dose group 44 +/- 6.5% (P < 0.05 versus controls), and for the high-dose group 76 +/- 5.3% (P < 0.001 versus controls and low-dose). Although coronary vascular resistance at the end of reperfusion showed no difference, mean coronary vascular resistance early after reperfusion was significantly lower (P < 0.0001) in both delapril groups than in control. In the high-dose group, reperfusion with L-NAME significantly increased coronary vascular resistance after ischemia/reperfusion and attenuated the cardioprotectiveness of delapril (P < 0.05 versus without nitro-L-arginine methyl ester). We thus found that oral administration of delapril was cardioprotective dose-dependently against ischemia/reperfusion injury. Nitric oxide appeared to be involved in the mechanism behind this cardioprotective effect.

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Beneficial Effects of Angiotensin I Converting Enzyme Inhibitor on Post-ischemic Contractile Function of Perfused Rat Heart

Cited by 13 publications

References 0 publications

Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass

Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass

Effects of long‐term treatment with trandolapril on sarcoplasmic reticulum function of cardiac muscle in rats with chronic heart failure following myocardial infarction

Cardioprotective effect of orally administered angiotensin-converting enzyme inhibitor against ischemia

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