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.