Transgenic overexpression of cardiac A1 adenosine receptors mimics ischemic preconditioning
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The role of A1adenosine receptors (A1AR) in ischemic preconditioning was investigated in isolated crystalloid-perfused wild-type and transgenic mouse hearts with increased A1AR. The effect of preconditioning on postischemic myocardial function, lactate dehydrogenase (LDH) release, and infarct size was examined. Functional recovery was greater in transgenic versus wild-type hearts (44.8 ᠳ.4% baseline vs. 25.6 ᠱ.7%). Preconditioning improved functional recovery in wild-type hearts from 25.6 ᠱ.7% to 37.4 ᠲ.2% but did not change recovery in transgenic hearts (44.8 ᠳ.4% vs. 44.5 ᠳ.9%). In isovolumically contracting hearts, pretreatment with selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine attenuated the improved functional recovery in both wild-type preconditioned (74.2 ᠷ.3% baseline rate of pressure development over time untreated vs. 29.7 ᠷ.3% treated) and transgenic hearts (84.1 ᠱ2.8% untreated vs. 42.1 ᠶ.8% treated). Preconditioning wild-type hearts reduced LDH release (from 7,012 ᠱ,451 to 1,691 ᠱ,256 U 砬-1 砧-1 砭in-1) and infarct size (from 62.6 ᠵ.1% to 32.3 ᠱ1.5%). Preconditioning did not affect LDH release or infarct size in hearts overexpressing A1AR. Compared with wild-type hearts, A1AR overexpression markedly reduced LDH release (from 7,012 ᠱ,451 to 917 ᠱ,123 U 砬-1 砧-1 砭in-1) and infarct size (from 62.6 ᠵ.1% to 6.5 ᠲ.1%). These data demonstrate that murine preconditioning involves endogenous activation of A1AR. The beneficial effects of preconditioning and A1AR overexpression are not additive. Taken with the observation that A1AR blockade equally eliminates the functional protection resulting from both preconditioning and transgenic A1AR overexpression, we conclude that the two interventions affect cardioprotection via common mechanisms or pathways.
American Journal of Physiology: Heart and Circulatory Physiology
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