title: K(ATP) channels and MPTP are involved in the cardioprotection bestowed by chronic intermittent hypobaric hypoxia in the developing rat.
abstract: The aim of this study was to explore the mechanism underlying the cardioprotection bestowed by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in developing rats. Neonatal male rats were subjected to CIHH treatments that simulated an altitude of 3000 m a.s.l. for 28 days (CIHH28) and 42 days (CIHH42), respectively, or no treatment (control). The left ventricular function of isolated hearts was evaluated. The ultra-microstructure, superoxide dismutase (SOD) activity and total anti-oxidation capacity (TAC) of the myocardium were determined. The basic left ventricular function remained unchanged in CIHH rats, except for an increased coronary flow. The recovery of cardiac function from I/R, however, was much better in CIHH rats than in control rats. Compared to control rats, CIHH rats had much higher SOD levels and TAC, and the ultra-microstructure damage to mitochondria was considerably less. The cardiac protection of CIHH was canceled out by glibenclamide, an inhibitor of the ATP-sensitive potassium (K(ATP)) channel, 5-hydroxydecanoate, an inhibitor of mitochondrial K(ATP) (mitoKATP), and atractyloside, an opener of the mitochondrial permeability transition pore (MPTP). To the contrary, diazoxide, an opener of mitoKATP, and cyclosporin A, a blocker of MPTP opening, induced cardioprotection in control rats. These results suggest that CIHH protects the heart against I/R injury in developing rats through opening of the K(ATP) channel and inhibiting of opening of the MPTP.
authors: Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China.
authors: Hui-min
authors: HM
authors: Bu
authors: Chang-ying
authors: CY
authors: Yang
authors: Mei-ling
authors: ML
authors: Wang
authors: Hui-jie
authors: HJ
authors: Ma
authors: Hong
authors: H
authors: Sun
authors: Yi
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D001274:Atmospheric Pressure; D001278:Atractyloside / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D001278:Atractyloside; C052853:5-hydroxydecanoic acid; D016572:Cyclosporine; D013482:Superoxide Dismutase; D003981:Diazoxide; D005905:Glyburide