Nitric oxide synthase protects the heart against ischemia-reperfusion injury in rabbits.
The role of nitric oxide (NO) in myocardial ischemia-reperfusion injury is still controversial. To determine the role of NO in the propagation of myocardial injury in a coronary artery occlusion-reperfusion model, we examined the effect of a competitive NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), with and without L-arginine, on the size of the infarct resulting from coronary artery occlusion (30 min) followed by reperfusion (48 hr) in rabbits. L-NAME (300 micrograms/kg, as a bolus, and 100 micrograms/kg/min, i.v.) with and without L-arginine (30 mg/kg, as a bolus, and 10 mg/kg/min, i.v.) was administered immediately before coronary occlusion to 60 min after reperfusion. The infarct size in the L-NAME-treated rabbits (75.1% +/- 5.0%, n = 7), assessed as a percentage of infarcted region/ischemic region, was significantly larger than that of control rabbits (51.2% +/- 7.4%, n = 7; P < .05). The increase in infarct size was significantly attenuated by the treatment with L-NAME and L-arginine (62.0% +/- 4.0%, n = 7). However, the infarct size for the treatment with L-NAME and D-arginine (76.7% +/- 5.7%, n = 6) did not differ from that in the L-NAME-treated rabbits. There was no significant difference in the infarct size between L-arginine-treated (60.1% +/- 7.3%, n = 6) and control rabbits. Rate-pressure products, as an index of myocardial oxygen consumption, were comparable in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hoshida
S
S
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Yamashita
N
N
Igarashi
J
J
Nishida
M
M
Hori
M
M
Kamada
T
T
Kuzuya
T
T
Tada
M
M
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D011817:Rabbits
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester