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: Rachael J Cerniway, R Ray Morrison, Anne M Byford, Amy R Lankford, John P Headrick, David G L Van Wylen, G Paul Matherne
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 97 Issue 3 Pg. 232-8 (May 2002) ISSN: 0300-8428 [Print] Germany
• PMID: 12061393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Decanoic Acids
• Hydroxy Acids
• Potassium Channels
• Receptors, Purinergic P1
• 5-hydroxydecanoic acid
• Adenosine Triphosphate
• Oxygen

Topics

• Adenosine Triphosphate (physiology)
• Animals
• Decanoic Acids (pharmacology)
• Female
• Heart (drug effects, physiopathology)
• Hydroxy Acids (pharmacology)
• Hypoxia (physiopathology)
• In Vitro Techniques
• Male
• Mice
• Mice, Transgenic (genetics)
• Mitochondria, Heart (metabolism)
• Myocardial Stunning (physiopathology)
• Oxygen (pharmacology)
• Potassium Channels (drug effects, metabolism)
• Rats
• Receptors, Purinergic P1 (genetics, metabolism)