Mechanisms of the Effects of Nicorandil in the Isolated Rat Heart During Ischemia and Reperfusion: A 31P-Nuclear Magnetic Resonance Study

Nicorandil (SG75) is a potent K+-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K+-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandil-containing (100, 300, or 1000 μM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10−3 M), nicorandil reduced ATP depletion during ischemia by 26% compared with untreated hearts. Blockade of K+ channels by glibenclamide prevented this protective effect. At all doses (10−4 to 10−3 M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 ± 0.03 vs. 6.02 ± 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K+ channels by glibenclamide. Hearts treated with nitroglycer...