Related Experiment Videos
Plasma nitric oxide end products are increased in the ischemic canine heart
1First Department of Medicine, Osaka University School of Medicine, Japan.
Insights
During myocardial ischemia and reperfusion, nitric oxide (NO) production increases, mediated by nitric oxide synthase. This NO release helps reduce coronary vascular resistance and lessen heart damage.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Nitric Oxide Metabolism
Background:
- Nitric oxide (NO) plays a crucial role in regulating vascular tone and myocardial function.
- Understanding NO metabolism during ischemic events is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of nitric oxide synthase (NOS) in myocardial ischemia and reperfusion.
- To quantify changes in stable NO metabolites (nitrate and nitrite) in response to reduced coronary blood flow.
Main Methods:
- Induction of myocardial ischemia in canine models with varying degrees of coronary blood flow reduction.
- Measurement of plasma nitrate and nitrite concentrations.
- Pharmacological inhibition of NOS using NG-nitro-L-arginine methyl ester (L-NAME) and subsequent L-arginine administration.
Main Results:
- Coronary arteriovenous difference for nitrate and nitrite increased significantly in ischemic hearts.
- Plasma nitrate+nitrite levels rose in direct correlation with the severity of coronary blood flow reduction.
- Reperfusion further elevated plasma nitrate+nitrite concentrations.
- L-NAME administration decreased both nitrate+nitrite production and coronary blood flow, effects reversed by L-arginine.
Conclusions:
- Increased nitric oxide production during myocardial ischemia and reperfusion is mediated by nitric oxide synthase.
- Elevated NO levels contribute to decreased coronary vascular resistance.
- This NO-mediated vasodilation helps attenuate myocardial ischemia and reperfusion injury.
Abstract:
Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.