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


RESULTS
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).


CONCLUSIONS
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.
Hui
Yue
Y
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192, Japan.
Mochizuki
Toshiaki
T
Kondo
Kazunao
K
Umemura
Kazuo
K
Sato
Shigehito
S
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D014325:Tromethamine / Q000494:pharmacology
C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D006834:Hydrazines; C074097:Krebs-Henseleit solution; D020030:Nitric Oxide Donors; D014325:Tromethamine; D000249:Adenosine Monophosphate; D006157:Guanosine Monophosphate; D005947:Glucose