noc-7 and Myocardial-Ischemia

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.. 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).. 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).. 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.

Topics: Animals; Cyclic GMP; Dose-Response Relationship, Drug; Heart; Hydrazines; Male; Myocardial Contraction; Myocardial Ischemia; Myocardium; Nitric Oxide Donors; Rats; Rats, Sprague-Dawley; Signal Transduction

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.. 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 microM, 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.. NOC7 at 2 and 20 microM 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 microM 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 x mg(-1) protein in the ischemic control group to 1.79 +/- 0.39, 1.86 +/- 0.25, and 2.63 +/- 0.24 pmol x mg(-1) protein, in the groups with NOC7 at 2, 20, and 200 microM, respectively (P < 0.05). The cGMP level increased from 1.49 +/- 0.61 pmol x mg(-1) protein in the ischemic control group to 3.92 +/- 0.66 pmol x mg(-1) protein in the group with NOC7 at 200 microM alone (P < 0.05).. 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.

Topics: Adenosine Monophosphate; Animals; Glucose; Guanosine Monophosphate; Hydrazines; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide Donors; Random Allocation; Rats; Rats, Sprague-Dawley; Research Design; Tromethamine