Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes

R. Ray Morrison, Bunyen Teng, Peter J. Oldenburg, Laxmansa C. Katwa, Jurgen B. Schnermann, S. Jamal Mustafa

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

To examine ischemic tolerance in the absence of A1 adenosine receptors (A1ARs), isolated wild-type (WT) and A1AR knockout (A1KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A 1AR deletion and/or ischemia-reperfusion. A1KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A1AR deletion. After 20 min of ischemia, CF was attenuated in A1KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A1KO hearts (54.4 ± 5.1 vs. WT 81.1 ± 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A1KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A1AR transcript in A1KO hearts, and the message for A2A, A2B, and A3 adenosine receptors was similar in uninstrumented A1KO and WT hearts. Ischemia-reperfusion increased A2B mRNA expression 2.5-fold in both WT and A1KO hearts without changing A1 or A3 expression. In WT hearts, ischemia transiently doubled A2A mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A1KO hearts. Together, these data affirm the cardioprotective role of A 1ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts.

Original languageEnglish (US)
Pages (from-to)H1875-H1882
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number4
DOIs
StatePublished - 2006

Keywords

  • Coronary flow
  • Gene expression
  • Lactate dehydrogenase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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