Delayed 24 hours Nomega-nitro-L-arginine methyl ester injection induces pharmacological cardioprotection against reperfusion injury.

Abstract

Previous studies indicate that adenosine supplementation or nitric oxide synthase (NOS) inhibition during reperfusion exert protective effects against myocardial ischemia-reperfusion (I/R) injury. We wanted to test the hypothesis that NOS inhibition before I/R also protects the myocardium against further injury and aimed to determine the involvement of adenosine receptors in a perfused rat heart model. Rats were injected with 10 mg/kg of L-NAME (N(omega)-nitro-L-arginine methyl ester) or L-NAME + SPT (8-(p-sulfophenyl)-theophylline)--an adenosine antagonist - at 2 x 25 mg/kg or with a saline buffer, 24 hrs prior to heart excision. The hearts, perfused retrogradely were subjected to 60 min of global ischemia followed by 120 min reperfusion. L-NAME decreased NOx (nitrite and nitrate) production (16.2 +/- 3.2 vs. 7.0 +/- 1.8 micromol/L; P<0.05) in vivo and increased the release of troponin I (0.04 +/- 0.01 vs. 0.02 +/- 0.01 microg/L; P<0.05) in the plasma, compared to controls. After 120 min of reperfusion, there was a higher release of adenosine (26.1 +/- 2.2 vs. 2.4 +/- 1.2 nmol/min; P<0.01) and a decrease in troponin I levels (0.19 +/-0.07 vs. 0.59 +/- 0.16 ng/min; P<0.05) in the L-NAME group compared to controls. These results were accompanied by a higher proportion of recovery of left ventricular developed pressure (72.0 +/- 4.0 vs. 60.0 +/- 4.0%; P<0.05) and coronary flow (72.0 +/- 5.0 vs. 51.0 +/- 4.0%; P<0.05) in the L-NAME group. These beneficial effects were not blocked by the adenosine receptor antagonist. The present study reveals that L-NAME protects against I/R injury when the inhibitor is administered 24 hrs before ischemia. The beneficial effects observed in this model appear to be independent of adenosine receptor stimulation.

• Authors: S Davani, C Vergely, B Royer, M Bouhaddi, H Reyssie, L Rochette, J P Kantelip
• Journal: Cellular and molecular biology (Noisy-le-Grand, France) (Cell Mol Biol (Noisy-le-grand)) Vol. 52 Suppl Pg. OL868-73 (Jan 21 2007) ISSN: 1165-158X [Electronic] France
• PMID: 17543224 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cardiotonic Agents
• Enzyme Inhibitors
• Nitrates
• Nitrites
• Troponin I
• arginine methyl ester
• Arginine
• Theophylline
• Nitric Oxide Synthase
• Adenosine

Topics

• Adenosine (blood, metabolism)
• Animals
• Arginine (administration & dosage, analogs & derivatives, pharmacology)
• Blood Pressure (drug effects)
• Cardiotonic Agents (administration & dosage, pharmacology)
• Disease Models, Animal
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Myocardial Ischemia (etiology)
• Myocardial Reperfusion Injury (prevention & control)
• Nitrates (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitrites (metabolism)
• Perfusion
• Rats
• Regional Blood Flow (drug effects)
• Theophylline (pharmacology)
• Time Factors
• Troponin I (blood, metabolism)
• Ventricular Function, Left (drug effects)