Nitric oxide donor,NOC7, reveals dose dependently and cGMP pathway independently biphasic effects on contractile force of isolated rat heart after global ischemia

Purpose: Our purpose was to investigate whether the 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), an ideal NO donor was dose dependently and cGMP-independent in restored cardiac function after global ischemia in an isolated rat heart model. Methods: Langendorff preparations of an isolated rat heart model were established. Isolated rat hearts (n = 40) were randomly divided into 5 groups (ischemic control group, NOC7 groups and NOC7+NS2028 groups). All groups were subjected to 35 min global ischemia, followed by 30 min reperfusion with Krebs-Henseleit bicarbonate buffer (KHB), and NOC7, NOC7+NS2028 at 2 and 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flows were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA). Results: 30 min of global ischemia increased LVDP to 121.9±11.5% at 35 min of reperfusion of 2 μM NOC7 group and 2 μM NOC7 associated with NS2028 group from the ischemic control group (P < 0.05). While in 200 μM NOC7 group and 200 μM NOC7 associated with NS2028 group, the LVDP value only slightly reduced, resulting in a value of only 45.3±10.4% and 35.3±6.0% of baseline (P > 0.05). Conclusion: NOC7 has biphasic effect on isolated rat heart after ischemia and reperfusion myocardial contractility. This biphasic effect shows neither concentration-dependent nor the cGMP-dependent characteristics.