Intrinsic activation of A1 adenosine receptors during ischemia and repurfusion improves ischemic tolerance
We assessed the role of A1 adenosine receptor (A1AR) activation by endogenous adenosine in the modulation of ischemic contracture and postischemic recovery in Langendorff-perfused mouse hearts subjected to 20 min of total ischemia and 30 min of reperfusion. In control hearts, the rate-pressure product (RPP) and first derivative of pressure development over time (+dP/dt) recovered to 57 ᠳ and 58 ᠳ% of preischemia, respectively. Diastolic pressure remained elevated at 20 ᠲ mmHg (compared with 3 ᠱ mmHg preischemia). Interstitial adenosine, assessed by microdialysis, rose from ~0.3 to 1.9 占during ischemia compared with ~15 占in rat heart. Nonetheless, these levels will near maximally activate A1ARs on the basis of effects of exogenous adenosine and 2-chloroadenosine. Neither A1AR blockade with 200 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) during the ischemic period alone nor A1AR activation with 50 nMN 6-cyclopentyladenosine altered rapidity or extent of ischemic contracture. However, ischemic DPCPX treatment significantly depressed postischemic recovery of RPP and +dP/dt (44 ᠳ and 40 ᠴ% of preischemia, respectively). DPCPX treatment during the reperfusion period alone also reduced recovery of RPP and +dP/dt (to 44 ᠲ and 47 ᠲ% of preischemia, respectively). These data indicate that1) interstitial adenosine is lower in mouse versus rat myocardium during ischemia, 2) A1AR activation by endogenous adenosine or exogenous agonists does not modify ischemic contracture in murine myocardium, 3) A1AR activation by endogenous adenosine during ischemia attenuates postischemic stunning, and 4) A1AR activation by endogenous adenosine during the reperfusion period also improves postischemic contractile recovery.
American Journal of Physiology: Heart and Circulatory Physiology
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