Effects of the AT1 Receptor Blocker Candesartan on Myocardial Ischemia/Reperfusion in Isolated Rat Hearts
Background: We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model.
Methods: Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated.
Results: In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant.
Conclusion: In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.
De Rosa ML. 2010. Cardio classics revisited-focus on the role of candesartan.Vasc Health Risk Manag 6:1047-63.nDzau VJ. 1994.Cell biology and genetics of angiotensin in cardiovascular disease. J Hypertens12:S3.nFukumoto T, Tawa M, Kitada K, et al. 2012. Different effects of AT1 receptor antagonist and ET(A) receptor antagonist on ischemia-induced norepinephrine release in rat hearts. J Cardiovasc Pharmacol 60:55-60.nGurevitch J, Pevni D, Frolkis I, et al. Captopril in cardioplegia and reperfusion: protective effects on the ischemic heart. Ann Thorac Surg 63:627-33.nHartman JC, Wall TM, Hullinger TG, Shebuski RJ. 1993. Reduction of myocardial infarct size in rabbits by ramiprilat: reversal by the bradykinin antagonist HOE 140. J Cardiovasc Pharmacol 21:996-1003.nJalowy A, Schulz R, Dorge H, et al. 1998. Infarct size reduction by AT1-receptor blockade through a signal cascade of AT2-receptor activation, bradykinin and prostaglandins in pigs. J Am Coll Cardiol 32:1787-96.nLeva C, Mariscalco G, Ferrarese S, et al. 2006. The role of zofenopril in myocardial protection during cardioplegia arrest: an isolated rat heart model. J Card Surg 21:44-9.nLiu YH, Yang XP, Sharov VG, et al. 1996. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats. Hypertension 27:7-13.nLucchese G, Cambi GE, Rita FD, et al. 2011. Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes. Artif Organs 35:1075-81.nMuller DN, Dechend R, Mervaala EM, et al. 2000. NF-kappa B inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension 35:193-201.nPaz Y, Gurevitch J, Frolkis I, et al. 1998. Effects of an angiotensin II antagonist on ischemic and nonischemic isolated rat hearts. Ann Thorac Surg 65:474-79.nRipley TL, Chonlahan JS, Germany ER. 2006. Candesartan in heart failure. Clin Interv Aging 1:357-66.nVanderheyden PML, Fierens FLP, Vauquelin G. 2000. Angiotensin II type 1 receptor antagonists. Why do some of them produce insurmountable inhibition? Biochem Pharmacol 60:1557.nVauquelin G, Fierens FLP, Vanderheyden PML. Distinction between surmountable and insurmountable angiotensin II AT1 receptor antagonists. In: Epstein M, Brunner HR, eds. Angiotensin II receptor antagonists. Philadelphia, PA: Hanley and Belful; 2000:105-18.nWeidenbach R, Schulz R, Gres P, et al. 2000. Enhanced reduction of myocardial infarct size by combined ACE inhibition and AT(1)-receptor antagonism. Br J Pharmacol 131:138-44.n
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