Cardioprotection in Brown Norway Rats is Linked to Mitochondrial Complex I Preservation

Abstract

Hearts from Brown Norway (BN) rats are more resistant to ischemia-reperfusion (IR) injury than hearts from Dahl Salt Sensitive (SS) rats. Moreover, introgression of BN chromosome 6 into SS confers IR resistance to the same degree as BN. We hypothesize that mitochondrial complex I preservation is linked to cardioprotection in this consomic rat model. Langendorff-prepared hearts from eight week old male BN, SS6BN and SS rats were subjected to 20 min perfusion, 30 min global ischemia or no ischemia (control), and 30 min reperfusion. Mitochondria were isolated and mitochondrial complex I preservation was measured by Western blotting using complex I NDUFA9 subunit antibody. We found higher protein levels in ischemic BN and SS6BN rat mitochondria compared to SS suggesting better preservation of complex I in BN and SS6BN. In contrast, the non-ischemic groups showed no detectable difference in protein levels. Previous studies have shown that mitochondrial function can be a trigger as well as an effector of cardioprotection. Our data shows that mitochondrial complex I is better preserved in BN and SS6BN than in SS. Since myocardial and mitochondrial functions differ significantly between the more IR-susceptible SS and the more IR-resistant BN and SS6BN strains, this suggests that rat chromosome 6 encodes one or more genes that are critical for mitochondrial function and cardioprotection.