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Nitric oxide synthase protects the heart against ischemia-reperfusion injury in rabbits
S Hoshida1, N Yamashita, J Igarashi
1First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Abstract:
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)
Insights
Nitric oxide (NO) inhibition worsened heart attack injury in rabbits. Supplementing with L-arginine reversed this damage, highlighting NO
Area of Science:
- Cardiovascular Science
- Pharmacology
- Cellular Biology
Background:
- The role of nitric oxide (NO) in myocardial ischemia-reperfusion injury remains debated.
- Understanding NO's function is crucial for developing effective treatments for heart attack damage.
Purpose of the Study:
- To investigate the specific role of NO in myocardial injury following coronary artery occlusion and reperfusion.
- To assess the impact of inhibiting NO synthesis on infarct size in a rabbit model.
Main Methods:
- Utilized a rabbit model of coronary artery occlusion (30 min) followed by reperfusion (48 hr).
- Administered NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, with and without L-arginine or D-arginine.
- Quantified infarct size as a percentage of the ischemic region.
Main Results:
- L-NAME treatment significantly increased infarct size compared to controls (75.1% vs. 51.2%).
- Co-administration of L-arginine with L-NAME significantly reduced infarct size (62.0%), attenuating the injury.
- D-arginine did not alter the infarct-size-increasing effect of L-NAME.
Conclusions:
- Inhibition of NO synthesis exacerbates myocardial ischemia-reperfusion injury.
- Supplementation with L-arginine can protect against NO inhibition-induced myocardial damage.
- These findings underscore the protective role of NO in the context of heart attack injury.