LACK OF A PHARMACOLOGICAL INTERACTION BETWEEN ATP-SENSITIVE POTASSIUMCHANNELS AND ADENOSINE A(1) RECEPTORS IN ISCHEMIC RAT HEARTS

Objectives: An interaction between adenosine A(1) receptors and ATP-se nsitive potassium channels (K-ATP) has been hypothesized to mediate pr econditioning in several species. Unlike other species tested, K-ATP b lockers and A(1) antagonists do not abolish preconditioning in rat hea rts. The purpose of this study was to determine if K-ATP and A(1) rece ptors are pharmacologically linked in rat hearts as they are in other species. Methods: Isolated rat hearts were given 0.03-1.00 mu M R-PIA (adenosine A(1) receptor agonist) with or without concomitant 0.3 mu M glyburide starting 10 min pre-ischemia. After 25 min global ischemia, the hearts were reperfused for 30 min. Rat hearts were also treated w ith 1-30 mu M cromakalim in the presence of 10 mu M DPCPX (adenosine A (1) antagonist). Results: R-PIA produced a concentration-dependent bra dycardia before ischemia which was blocked by DPCPX. R-PIA increased t he time to onset of contracture in a concentration-dependent manner (E C(25) = 0.13 mu M) and this was unaffected by 0.3 mu M glyburide (EC(2 5) = 0.20 mu M). This concentration of glyburide completely abolished the protective effects of 10 mu M cromakalim. R-PIA also significantly enhanced post-ischemic recovery of function and reduced LDH release, and glyburide did not alter these responses. Cromakalim significantly increased the time to onset of contracture (EC(25) = 4.5 mu M) and 10 mu M DPCPX had no effect on this (EC(25) = 5.6 mu M). Cromakalim also significantly enhanced post-ischemic recovery of function and reduced LDH release. DPCPX did not alter these cardioprotective effects while glyburide completely abolished the cardioprotective effects of cromaka lim. Conclusions: While both cromakalim and R-PIA are cardioprotective in isolated rat hearts, they are not pharmacologically linked, possib ly explaining why preconditioning may be different in this species.