title: A1 adenosine receptor overexpression decreases stunning from anoxia-reoxygenation: role of the mitochondrial K(ATP) channel.
abstract: Myocardial A1 adenosine receptor (A1AR) overexpression protects hearts from ischemia-reperfusion injury; however, the effects during anoxia are unknown. We evaluated responses to anoxia-reoxygenation in wild-type (WT) and transgenic (Trans) hearts with approximately 200-fold overexpression of A1ARs. Langendorff perfused hearts underwent 20 min anoxia followed by 30 min reoxygenation. In WT hearts peak diastolic contracture during anoxia was 45+/-3 mmHg, diastolic pressure remained elevated at 18+/-3 mmHg after reoxygenation, and developed pressure recovered to 52+/-4% of pre-anoxia. A1AR overexpression reduced hypoxic contracture to 29+/-4 mmHg, and improved recovery of diastolic pressure to 8+/-1 mmHg and developed pressure to 76+/-3% of pre-anoxia. Mitochondrial K(ATP) blockade with 100 microM 5-hydroxydecanoate (5-HD) increased hypoxic contracture to 73+/-6 mmHg in WT hearts, reduced post-hypoxic recoveries of both diastolic (40+/-5 mmHg) and developed pressures (33+/-3 %). In contrast, 5-HD had no effect on hypoxic contracture (24+/-8 mmHg), or post-hypoxic diastolic (10+/-2 mmHg) and developed pressures (74+/-3%) in Trans hearts. In summary, (i) A1AR overexpression improves myocardial tolerance to anoxia-reoxygenation, (ii) intrinsic mitochondrial K(ATP) channel activation decreases hypoxic contracture and improves functional recovery in wild-type hearts, and (iii) mitochondrial K(ATP) channels do not appear to play a major role in the functional protection from anoxia afforded by A1AR overexpression.
authors.affiliation: Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Cerniway
authors.forename: R Ray
authors.initials: RR
authors.lastname: Morrison
authors.forename: Anne M
authors.initials: AM
authors.lastname: Byford
authors.forename: Amy R
authors.initials: AR
authors.lastname: Lankford
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
authors.forename: David G L
authors.initials: DG
authors.lastname: Van Wylen
authors.forename: G Paul
authors.initials: GP
authors.lastname: Matherne
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008929:Mitochondria, Heart / Q000378:metabolism*; D017682:Myocardial Stunning / Q000503:physiopathology*; D010100:Oxygen / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D010100:Oxygen