Cardioprotective effect of postconditioning against ischemia-reperfusion injury is lost in heart of 8-week diabetic rat.

Although ischemic preconditioning (IPC) and ischemic postconditioning (IPost) result in protection against ischemia-reperfusion (I/R) injury in healthy hearts, pathological conditions such as diabetes can modify the protective effects of IPC and IPost. There are a few studies concerning the effect of IPost only in diabetic hearts which have similar or decreased tolerance to I/R injury. In the present study we investigated the effects of IPost in diabetic hearts which had increased tolerance to I/R injury. Isolated hearts from control and diabetic rats were subjected to global ischemia (40 min) followed by reperfusion (40 min). IPost was induced by six cycles (10 s) of reperfusion and ischemia after the global ischemia. After I/R, cardiac recovery in diabetic hearts was better than that in control hearts. IPost did not produce any further protection in the diabetic hearts whereas it resulted in a significant recovery in the control hearts. Similarly, the decreased troponin I (TnI) levels of diabetic hearts did not change after IPost. However, IPost significantly lowered the increase in TnI levels of control hearts. In conclusion, these results show that IPost can not produce a further protection in the hearts of 8-week diabetic rats which have increased tolerance to I/R injury.

ß3-Adrenoceptor-mediated responses in diabetic rat heart.

ß3-adrenoceptors mediate negative inotropic effect in contrast to classical ß1- and ß2-adrenoceptors. Cardiac ß3-adrenoceptors are upregulated in experimental diabetes. Thus, cardiodepressant effect mediated by ß3-adrenoceptors has been proposed to contribute to the impaired cardiac function in this pathology. In our study, we investigated the influence of streptozotocin-diabetes on cardiac contractility to ß3-adrenoceptors stimulation by using Langendorff-perfused rat hearts. BRL 37344, a selective ß3-adrenoceptor agonist, induced dose-dependent decreases in left ventricular developed pressure (LVDP) in hearts from control rats. BRL 37344 also dose-dependently decreased +dP/dt and -dP/dt values. Effects of BRL 37344 were abolished by SR 59230, but not altered by nadolol pre-treatment. On the other hand, these effects of BRL 37344 were all significantly increased in hearts from diabetic rats. We also observed that diabetes significantly increased the mRNA levels encoding cardiac ß3-adrenoceptors. In addition, Giα2 mRNA expressions were found to be increased in the cardiac tissue of diabetic rats as well. The effect of BRL 37344 on cardiac contractility was normalized upon treatment of diabetic rats with insulin. These data demonstrate an increased effect of ß3-adrenoceptor stimulation on hemodynamic function of the heart in accordance with an increased mRNA levels encoding cardiac ß3-adrenoceptors in 8-week diabetic rats.