L-arginine suppresses ischemia/reperfusion induced up-regulation of endothelin-1 production in a rat model of acute myocardial injury

Abstract

To examine the level of endothelin-1 (ET-1) in serum and its expression in myocardium tissue during the development of acute myocardial ischemia/reperfusion (I/R) injury in rat and the effects of L-arginine (L-Arg) administration on these indexes. One hundred and ten Wistar rats were randomly divided into nine groups to receive: (1) sham surgery, (2)ischemia (I, by ligation of anterior descending coronary artery for 30 minutes), (3) I+reperfusion (R, by the removal of the ligature) for 0.5 hour, (4) I+R for 1 hour, (5) I+R for 2 hours; group (6) ~ (9) also received I/R treatment as in group 2 ~ 5 respectively but with L-Arg pretreatment. Blood and myocardium tissue samples were collected by the end of the experiment for the analysis of: serum level of creatine kinase (CK), lactate dehydrogenase [LDH, by enzyme linked immunosorbent assay (ELISA)], ET-1 (radioimmunoassay), and the tissue content of ET-1 mRNA/peptide [by reverse-transcription polymerase chain-reaction (RT-PCR) and Western blotting]. In comparison with the sham treated control animals, the serum levels of CK, LDH, and ET-1 were all significantly higher in the groups treated with I/R (particularly those exposed to reperfusion). The myocardial tissue content of ET-1 mRNA/peptide were also significantly increased in I/R treated groups (particularly the I+R 2 hours group) as compared to control (ET-1 mRNA: 0.775 ± 0.029 vs. 0.310 ± 0.076; ET-1 peptide: 0.773 ± 0.055 vs. 0.340 ± 0.099, both P < 0.05). The i.v. administration of L-Arg significantly suppressed the up-regulation of tissue content of ET-1 mRNA /peptide in I/R treated animals (ET-1 mRNA: 0.340 ± 0.049 vs. 0.775 ± 0.029; ET-1 peptide: 0.390 ± 0.094 vs. 0.773 ± 0.055, both P < 0.05). L-Arg may be tested during certain stage of I/R injury as a therapeutic intervention for the suppression of ET-1 up-regulation.