Possible role of mitochondrial K-ATP channel and nitric oxide in protection of the neonatal rat heart

Abstract

Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff. Developed force (DF) of contraction was measured. Hearts were exposed to 40 min of global ischemia followed by reperfusion up to the maximum recovery of DF. IPoC was induced by 5 cycles of 10-s ischemia. Mito-K-ATP blocker (5-HD) was administered 5 min before ischemia and during first 20 min of reperfusion. Another group of hearts was isolated for biochemical analysis of 3-nitrotyrosine, and serum samples were taken to measure nitrate levels. Tolerance to ischemia did not change from day 1 to day 4 but decreased on days 7 and 10. 5-HD had no effect either on neonatal resistance to I/R injury or on cardioprotective effect of IPoC on day 10. Significant difference was found in serum nitrate levels between days 1 and 10 but not in tissue 3-nitrotyrosine content. It can be concluded that while there appears to be significant difference of NO production, mito-K-ATP and ROS probably do not play role in the high neonatal resistance to I/R injury.

Effects of a mitochondrial-acting drug on ischemia/reperfusion-induced ventricular arrhythmias, cardiac mitochondrial function and inflammatory cytokines in rat: Role of adenosine triphosphate-sensitive potassium channels

“…Finally, it is believed that NO can have protective impacts on the IR hearts by opening these channels. 19 In this study, although the drug increased the production of NO metabolites, inhibition of mK-ATP channels by 5HD could not reverse this effect, indicating that the effect of KH176 therapy on myocardial NO production in IR hearts was not dependent on the opening of mK-ATP channels. Furthermore, the effect of KH176 on NO levels in the presence of 5HD indicates that NO production in this situation occurs upstream of these channels.…”

Changes in Endothelial Nitric Oxide Production in Systemic Vessels during Early Ontogenesis—A Key Mechanism for the Perinatal Adaptation of the Circulatory System

“…In the neonatal pig coronary circulation, NO was shown to exert a powerful anticontractile effect on basal tone and to mediate a substantial part of agonist-stimulated dilatory responses [22]. In the neonatal rat heart endogenous NO is protective against ischemia/reperfusion injury [23]. Of note, in coronary arteries from adult rats a strong augmentation of basal tone and contractile responses was demonstrated after treatment with a NOS inhibitor [24].…”