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Angiotensin II and Ischemic Preconditioning Synergize to Improve Mitochondrial Function While Showing Additive Effects on Ventricular Postischemic Recovery

Nuñez, Rebeca E. BS; Castro, Miriam BS; Javadov, Sabzali PhD, MD; Escobales, Nelson PhD

Journal of Cardiovascular Pharmacology: August 2014 - Volume 64 - Issue 2 - p 172–179
doi: 10.1097/FJC.0000000000000103
Original Article

Abstract: Recent studies indicate that the cardioprotective effects of ischemic preconditioning (IPC) against sustained ischemia/reperfusion can be replicated by angiotensin II (Ang II). However, it is not clear whether IPC and Ang II–induced preconditioning (APC) act through similar mechanisms or synergize to enhance cardioprotection. In this study, Langendorff-perfused rat hearts were subjected to IPC, APC, or their combination (IPC/APC) followed by ischemia/reperfusion. IPC, and less potently APC, significantly increased the percent recoveries of the left ventricular developed pressure, the first derivative of developed pressure, and the rate pressure product compared with control. Furthermore, the postischemic recovery of the heart was significantly higher for IPC/APC compared with IPC or APC. The improvements in cardiac function by IPC, APC, and IPC/APC were associated with similar reductions in lactate dehydrogenase release and infarct size. However, a significant improvement in mitochondrial respiration was observed with IPC/APC. The postischemic recovery observed with APC and IPC/APC was inhibited by treatment with losartan, an Ang II type-1 receptor blocker, during the preconditioning phase but not by chelerythrine, a pan-PKC inhibitor. Both drugs, however, abolished the enhanced mitochondrial respiration by IPC/APC. Altogether, these results indicate that APC and IPC interact through mechanisms that enhance cardioprotection by affecting cardiac function and mitochondrial respiration.

Department of Physiology, University of Puerto Rico School of Medicine, San Juan, PR.

Reprints: Nelson Escobales, PhD, Department of Physiology, University of Puerto Rico School of Medicine, PO Box 365067, San Juan, PR 00936-5067 (e-mail:

The authors report no conflicts of interest.

Supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health through Research Grant SC1HL118669 (S. Javadov) and, in part, by Research Centers in Minority Institutions (RCMI) grant G12MD007600 (National Institute on Minority Health and Health Disparities) from the National Institutes of Health.

Received August 26, 2013

Accepted March 24, 2014

© 2014 by Lippincott Williams & Wilkins.