A novel cardioprotective agent, JTV-519, is abolished by nitric oxide synthase inhibitor on myocardial metabolism in ischemia-reperfused rabbit hearts.

Abstract

We investigated the effect of a novel cardioprotective agent, JTV-519, with or without a nitric oxide synthase inhibitor, L-NAME, on the myocardial metabolism and contraction during ischemia and reperfusion by means of phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After 20 min normothermic global ischemia, postischemic reperfusion was carried out for 30 min. JTV-519 was administered from 40 min prior to the global ischemia. Twenty-one hearts were divided into three experimental groups consisting of 7 hearts each: a control group, a JTV-519 group perfused with JTV-519, and a JTV-519+L-NAME group perfused with a combination of JTV-519 and L-NAME. During ischemia, the JTV-519 group showed a significant inhibition of the decrease in adenosine triphosphate (ATP) compared with both the control and JTV-519+L-NAME groups (p<0.01); the levels of ATP were 20+/-6, 56+/-9, and 40+/-4% in the control group, JTV-519 group, and JTV-519+L-NAME group, respectively. Both the JTV-519 group and JTV-519+L-NAME group showed a significant inhibition of the increase in left ventricular end-diastolic pressure (LVEDP) compared with the control group (p<0.01). After postischemic reperfusion, the JTV-519 group again showed a significant improvement of ATP as compared with both the control and JTV-519+L-NAME groups (p<0.01); the ATP levels were 52+/-4, 82+/-3, and 64+/-3% in the control group, JTV-519 group, and JTV-519+L-NAME group. In conclusion, JTV-519 has a significant beneficial effect on myocardial energy metabolism during both ischemia and reperfusion. This beneficial effect was dependent on NO synthase. Furthermore, JTV-519 showed significant potential for improving myocardial relaxation during ischemia. This effect was not dependent on NO synthase.

• Authors: Hitoshi Kawabata, Kizuku Nakagawa, Kinji Ishikawa
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 25 Issue 2 Pg. 303-9 (Mar 2002) ISSN: 0916-9636 [Print] England
• PMID: 12047047 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Enzyme Inhibitors
• Thiazepines
• K201 compound
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Coronary Circulation
• Enzyme Inhibitors (pharmacology)
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Myocardial Ischemia (metabolism, physiopathology)
• Myocardial Reperfusion Injury (metabolism, physiopathology)
• Myocardium (metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Pressure
• Rabbits
• Thiazepines (pharmacology)
• Ventricular Function, Left