title: Chronic intermittent hypobaric hypoxia ameliorates ischemia/reperfusion-induced calcium overload in heart via Na/Ca2+ exchanger in developing rats.
abstract: OBJECTIVE
  Chronic intermittent hypobaric hypoxia (CIHH) protects the heart against ischemia/reperfusion (I/R) injury. This study investigated the calcium homeostasis mechanism and the role of Na(+)/Ca(2+) exchanger (NCX) in the cardiac protective effect of CIHH in developing rats.
  
  
  METHODS
  Neonatal male rats received CIHH treatment or no treatment (control) in a hypobaric chamber simulating 3000-meter altitude for 42 days. The left ventricular function of isolated hearts was evaluated after 30 minutes of ischemia and 60 minutes of reperfusion. Myocardial infarct size, intracellular Ca(2+) concentration ([Ca(2+)]i), Na(+)-Ca(2+) exchanger currents (I(Na/Ca)) in ventricular myocytes, and NCX1 protein level in the sarcolemmal membrane were determined.
  
  
  RESULTS
  The recovery of cardiac function after I/R was improved, with the myocardial infarct size reduced, in CIHH rats compared with control rats (p<0.05). These effects were attenuated by Bay K8644, an L-type Ca(2+) channel agonist, or ryanodine, a sarcoplasmic reticulum Ca(2+) channel receptor activator. Furthermore, the increases in [Ca(2+)]i during I/R were blunted in CIHH rats, but this effect was abolished by Bay K8644 or chelerythrine, a protein kinase C (PKC) inhibitor. The I(Na/Ca) was decreased and the reversal potential of INa/Ca was shifted toward negative potential during simulated ischemia in the control cardiomyocytes (p<0.05). The inhibition of NCX1 protein expression during I/R was smaller in the CIHH rats than in the control rats (p<0.05).
  
  
  CONCLUSIONS
  These data suggest that CIHH protects developing rat hearts during I/R by enhancing the resistance against calcium overload and by preserving normal I(Na/Ca) and NCX1 protein. PKC activation might be involved in this protective process of CIHH.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Ma
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
chemical_list: D019831:Sodium-Calcium Exchanger; D002118:Calcium