Key Points
- To determine whether ATP-sensitive potassium (KATP) channels and adenosine A1 receptors are pharmacologically coupled to mediate cardioprotection in ischemic rat hearts.
- Isolated rat hearts were subjected to 25 minutes of global ischemia followed by 30 minutes of reperfusion.
- Hearts were treated with the adenosine A1 agonist R-PIA (0.03–1.00 µM) with or without the KATP blocker glyburide (0.3 µM) starting 10 minutes prior to ischemia.
- Separate preparations received the KATP opener cromakalim (1–30 µM) with or without the adenosine A1 antagonist DPCPX (10 µM).
- R-PIA delayed the time to contracture onset (EC25 = 0.13 µM), improved functional recovery, and reduced LDH release, none of which were altered by 0.3 µM glyburide (EC25 = 0.20 µM).
- Cromakalim delayed contracture onset (EC25 = 4.5 µM), enhanced recovery, and lowered LDH release; 10 µM DPCPX failed to alter these effects (EC25 = 5.6 µM), whereas glyburide completely abolished cromakalim-induced cardioprotection.
Structured PICO
Are ATP-sensitive potassium channels and adenosine A1 receptors pharmacologically linked in mediating cardioprotection in isolated ischemic rat hearts?
PPopulationIsolated rat hearts subjected to 25 min global ischemia and 30 min reperfusion
IInterventionR-PIA (adenosine A1 receptor agonist) 0.03-1.00 microM with or without 0.3 microM glyburide; or cromakalim 1-30 microM with or without 10 microM DPCPX (adenosine A1 antagonist)
CComparatorRespective control conditions (R-PIA alone vs R-PIA + glyburide; cromakalim alone vs cromakalim + DPCPX)
OOutcomeTime to onset of contracture, post-ischemic recovery of function, and LDH releasesurrogate
In isolated rat hearts, the cardioprotective effects of adenosine A1 receptor agonists and ATP-sensitive potassium channel openers are not pharmacologically linked, which differs from other species.