Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels.
Brief renal ischemia-reperfusion is reported to precondition the myocardium; however, the underlying mechanisms are unknown. This phenomenon was, therefore, investigated using an in vivo rabbit model of acute myocardial infarction. Characterization of the mechanisms involved was performed using the nonselective adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-SPT) and the ATP-sensitive potassium (KATP) channel blocker sodium 5-hydroxydecanoate (5-HD). Pentobarbital-anesthetized rabbits underwent a left thoracotomy and pericardiotomy. A laparotomy was then performed to expose the left renal artery. Animals were either preconditioned with a 10-min occlusion of the renal artery followed by 10 min of reperfusion or underwent a 20-min sham period of anesthesia. Subsequently, the left coronary artery was then occluded for 30 min and reperfused for 2 h. Infarct-to-risk ratio was limited from 32.7 +/- 4.0% (n = 12) in controls to 17.8 +/- 3.0% (n = 9; P = 0.002) in preconditioned hearts. Protection was abolished by 7.5 mg/kg iv 8-SPT (36.7 +/- 3.7%; n = 6) or 5 mg/kg iv 5-HD (33.1 +/- 4. 4%; n = 6) administered before preconditioning. 8-SPT (40.0 +/- 4. 4%; n = 6) or 5-HD (40.5 +/- 4.2%; n = 6) did not affect infarct-to-risk ratio in sham controls. Thus activation of both adenosine receptors and KATP channels appears to be involved in acute renal preconditioning of the myocardium.
Pell
T J
TJ
The Hatter Institute for Cardiovascular Studies, University College London Hospitals and Medical School, London WC1E 6DB, United Kingdom.
Baxter
G F
GF
Yellon
D M
DM
Drew
G M
GM
D000818:Animals; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial; D007668:Kidney / Q000098:blood supply*; D015221:Potassium Channels / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline