Nitric oxide donor, NOC7, reveals biphasic effect on contractile force of isolated rat heart after global ischemia

Purpose: Our purpose was to investigate whether the NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), restored cardiac function following global ischemia in an isolated rat heart model and whether intracellular messengers were involved in its effect. Methods: Isolated rat hearts (n = 36) were randomly divided into six groups. The sham control group was perfused with modified Krebs-Henseleit bicarbonate buffer (KHB) alone. The ischemic control group and the NOC7 groups were subjected to 35 min of global ischemia, followed by 30 min of reperfusion with KHB alone, or reperfusion with KHB including NOC7 at 0.2, 2, 20, or 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flow were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA) methods. Results: NOC7 at 2 and 20 μM rescued myocardial performance (LVDP, 111.9 ± 10.5% and 124.3 ± 12.5% of baseline, respectively; P < 0.05 vs ischemic control) at 30 min after reperfusion. However, NOC7 at 200 μM reduced the LVDP to 55.3 ± 6.0% of baseline. Coronary flows remain unchanged. The cAMP levels increased significantly from 0.83 ± 0.44 pmol·mg^-1 protein in the ischemic control group to 1.79 ± 0.39, 1.86 ± 0.25, and 2.63 ± 0.24 pmol·mg^-1 protein, in the groups with NOC7 at 2, 20, and 200 μM, respectively (P < 0.05). The cGMP level increased from 1.49 ± 0.61 pmol·mg^-1 protein in the ischemic control group to 3.92 ± 0.66 pmol·mg^-1 protein in the group with NOC7 at 200 μM alone (P < 0.05). Conclusion: NOC7 appeared to exert a biphasic effect on the contractile force of the isolated rat heart after 35-min global ischemia. The balance between intracellular cAMP and cGMP levels seemed to be involved in its mechanism.