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Adenosine-A1 receptors activation restores the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts.
J Cardiovasc Pharmacol. 2009 Sep; 54(3):204-12.JC

Abstract

BACKGROUND

We have previously shown that the cardioprotective effect of ischemic preconditioning (IPC) is suppressed in hyperhomocysteinemic rat hearts. The present study investigated the effect of 2-chloro-N-cyclopentyladenosine (CCPA), a selective adenosine-A1 receptor agonist, in hyperhomocysteinemia-induced attenuation of the cardioprotective effect of IPC.

METHODS

Rats were administered L-methionine (1.7 g/kg/day po) for 8 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to 30-minute global ischemia, followed by a 120-minute reperfusion. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase and CK-MB release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid reactive substance and reduced form of glutathione.

RESULTS

Ischemia and reperfusion (I/R) produced myocardial injury by increasing myocardial infarct size, elevating lactate dehydrogenase and CK-MB release in coronary effluent, decreasing coronary flow rate, and inducing oxidative stress in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high oxidative stress. The IPC afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts. However, IPC-mediated myocardial protection against I/R injury was abolished in hyperhomocysteinemic rat hearts. Administration of CCPA did not alter the cardioprotective effect of IPC in normal rat hearts, but its administration markedly restored the cardioprotective effect of IPC in hyperhomocysteinemic rat hearts.

CONCLUSION

It may be concluded that the activation of adenosine-A1 receptors using CCPA markedly restored the suppressed cardioprotective and infarct size-limiting effects of IPC in hyperhomocysteinemic rat hearts. Thus, the reduced availability of extracellular adenosine and impaired activation of adenosine-A1 receptors may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury in hyperhomocysteinemic rat hearts.

Authors+Show Affiliations

Cardiovascular Pharmacology Division, ISF College of Pharmacy, Moga, Punjab, India. pbala2006@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19568176

Citation

Balakumar, Pitchai, et al. "Adenosine-A1 Receptors Activation Restores the Suppressed Cardioprotective Effects of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts." Journal of Cardiovascular Pharmacology, vol. 54, no. 3, 2009, pp. 204-12.
Balakumar P, Singh H, Reddy K, et al. Adenosine-A1 receptors activation restores the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts. J Cardiovasc Pharmacol. 2009;54(3):204-12.
Balakumar, P., Singh, H., Reddy, K., & Anand-Srivastava, M. B. (2009). Adenosine-A1 receptors activation restores the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts. Journal of Cardiovascular Pharmacology, 54(3), 204-12. https://doi.org/10.1097/FJC.0b013e3181b04cc5
Balakumar P, et al. Adenosine-A1 Receptors Activation Restores the Suppressed Cardioprotective Effects of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts. J Cardiovasc Pharmacol. 2009;54(3):204-12. PubMed PMID: 19568176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenosine-A1 receptors activation restores the suppressed cardioprotective effects of ischemic preconditioning in hyperhomocysteinemic rat hearts. AU - Balakumar,Pitchai, AU - Singh,Harsimran, AU - Reddy,Krishna, AU - Anand-Srivastava,Madhu B, PY - 2009/7/2/entrez PY - 2009/7/2/pubmed PY - 2010/8/19/medline SP - 204 EP - 12 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 54 IS - 3 N2 - BACKGROUND: We have previously shown that the cardioprotective effect of ischemic preconditioning (IPC) is suppressed in hyperhomocysteinemic rat hearts. The present study investigated the effect of 2-chloro-N-cyclopentyladenosine (CCPA), a selective adenosine-A1 receptor agonist, in hyperhomocysteinemia-induced attenuation of the cardioprotective effect of IPC. METHODS: Rats were administered L-methionine (1.7 g/kg/day po) for 8 weeks to produce hyperhomocysteinemia. Isolated Langendorff perfused normal and hyperhomocysteinemic rat hearts were subjected to 30-minute global ischemia, followed by a 120-minute reperfusion. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase and CK-MB release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid reactive substance and reduced form of glutathione. RESULTS: Ischemia and reperfusion (I/R) produced myocardial injury by increasing myocardial infarct size, elevating lactate dehydrogenase and CK-MB release in coronary effluent, decreasing coronary flow rate, and inducing oxidative stress in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with high oxidative stress. The IPC afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts. However, IPC-mediated myocardial protection against I/R injury was abolished in hyperhomocysteinemic rat hearts. Administration of CCPA did not alter the cardioprotective effect of IPC in normal rat hearts, but its administration markedly restored the cardioprotective effect of IPC in hyperhomocysteinemic rat hearts. CONCLUSION: It may be concluded that the activation of adenosine-A1 receptors using CCPA markedly restored the suppressed cardioprotective and infarct size-limiting effects of IPC in hyperhomocysteinemic rat hearts. Thus, the reduced availability of extracellular adenosine and impaired activation of adenosine-A1 receptors may be responsible for abolishing the cardioprotective potential of IPC against I/R-induced myocardial injury in hyperhomocysteinemic rat hearts. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/19568176/Adenosine_A1_receptors_activation_restores_the_suppressed_cardioprotective_effects_of_ischemic_preconditioning_in_hyperhomocysteinemic_rat_hearts_ L2 - https://doi.org/10.1097/FJC.0b013e3181b04cc5 DB - PRIME DP - Unbound Medicine ER -