Role of oxidative stress in PKC-δ upregulation and cardioprotection induced by chronic intermittent hypoxia

Abstract

The aim was to determine whether increased oxidative stress during the adaptation to chronic intermittent hypoxia (CIH) plays a role in the induction of improved cardiac ischemic tolerance. Adult male Wistar rats were exposed to CIH in a hypobaric chamber (7,000 m, 8 h/day, 5 days/wk, 24-30 exposures). Half of the animals received antioxidant N-acetylcysteine (NAC; 100 mg/kg) daily before the exposure; the remaining rats received saline. Control rats were kept under normoxia and treated in a corresponding manner. One day after the last exposure (and/or NAC injection), anesthetized animals were subject to 20 min of coronary artery occlusion and 3 h of reperfusion for determination of infarct size. In parallel subgroups, biochemical analyses of the left ventricular myocardium were performed. Adaptation to CIH reduced infarct size from 56.7 +/- 4.5% of the area at risk in the normoxic controls to 27.7 +/- 4.9%. NAC treatment decreased the infarct size in the controls to 42.0 +/- 3.4%, but it abolished the protection provided by CIH (to 41.1 +/- 4.9%). CIH decreased the reduced-to-oxidized glutathione ratio and increased the relative amount of PKC isoform-delta in the particulate fraction; NAC prevented these effects. The expression of PKC-epsilon was decreased by CIH and not affected by NAC. Activities of superoxide dismutase, catalase, and glutathione peroxidase were affected by neither CIH nor NAC treatment. It is concluded that oxidative stress associated with CIH plays a role in the development of increased cardiac ischemic tolerance. The infarct size-limiting mechanism of CIH seems to involve the PKC-delta-dependent pathway but apparently not the increased capacity of major antioxidant enzymes.

Chronic Intermittent Hypobaric Hypoxia Ameliorates Ischemia/Reperfusion-Induced Calcium Overload in Heart via Na+/Ca2+Exchanger in Developing Rats

“…Because CIHH preserves intracellular pH during I/R by PKC activation [42,43], it is possible that this mechanism mediates the suppression of I Na/Ca in CIHH-treated rats. Furthermore, it has been shown that an increase in cytosolic ATP stimulates I Na/Ca in cardiac myocytes [44].…”

Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca2+Handling in Neonatal Rat Cardiomyocytes

“…Previously, excess ROS accumulation was itself considered injurious because it can cause lipid peroxidation, protein oxidation, DNA damage [6] and intracellular ion deregulation [7], damaging cellular physiological function. However, it is generally accepted at present that ROS may exert beneficial actions [8] because short or moderate durations of ROS generation can result in pre-conditioning protection of the heart [9] against ischemia/reperfusion (I/R) injury [1]. This protective effect is partially due to IH-induced increases in antioxidative capacity for removing excess ROS [10] and improved Ca 2+ handling for attenuating cytosolic Ca 2+ overload [11].…”

CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

“…Both complexes produce reactive oxygen species (ROS) on the matrix side and ␤-oxidation of FA can lead to greater release of ROS, mainly from complex I (50). Although the involvement of ROS in protective signaling has been well documented (23,57), it is unknown whether it may play a role in the infarct size reduction in SHR-Cd36.…”