[Protective effect of urantide against myocardial ischemia injury].

Abstract

This study is to investigate the protective effect of urantide against myocardial ischemia injury in mice and its mechanism. The ischemic model was made by using subcutaneous injection of isoproterenol (Iso) in mice, the change of ST segment of electrocardiogram (ECG) was observed, and the activitise of lactate dehydrogenase (LDH) and nitric oxide synthetase (NOS), the contents of malonaldehyde (MDA) and nitric oxide (NO) in serum were measured. The histopathological changes of myocardium were observed by using HE staining. The anoxia/reoxygenation (A/R) model of myocardial cells on neonatal Sprague-Dawley rats was established. Methyl thiazolyl tetrazolium (MTT) assay and confocal microscopy were respectively used to measure the viability and intracellular Ca2+ concentration in myocardial cells exposed to A/R. LDH activity and cTnI content in the cell culture medium were assayed for the evaluation of myocardial cells injury. The results revealed that urantide in the range of 3 - 30 microg kg(-1) iv markedly inhibited Iso-induced raise of the ST segment of ECG; 10 and 30 microg kg(-1) significantly reduced the increases of MDA content and LDH activity in mice serum, remarkably raised the activity of NOS and the content of NO. Urantide (10 and 30 microg kg(-1)) also significantly ameliorated myocardial ischemic injury. On the A/R model of myocardial cells, urantide (1 x 10(-6) - 1 x 10(-9) mol L(-1)) could evidently inhibit the increases of cTnI content, reduce the rise of intracellular Ca2+ concentration. Urantide (1 x 10(-6) - 1 x 10(-7)) mol L(-1) increased the viability of myocardial cells injured by A/R and cut down LDH activity in the cell culture medium. Therefore urantide has significant protective effect against myocardial ischemia or A/R injury via the inhibition of Ca2+ overload and the augmentation of NO synthesis.

• Authors: Hu Yao, Zhi-Wu Chen
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 43 Issue 2 Pg. 150-6 (Feb 2008) ISSN: 0513-4870 [Print] China
• PMID: 18507341 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Peptide Fragments
• Troponin I
• Urotensins
• urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-
• Nitric Oxide
• Malondialdehyde
• L-Lactate Dehydrogenase
• Nitric Oxide Synthase
• Isoproterenol
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cardiotonic Agents (pharmacology)
• Cells, Cultured
• Electrocardiography
• Female
• Isoproterenol
• L-Lactate Dehydrogenase (blood)
• Male
• Malondialdehyde (blood)
• Mice
• Myocardial Ischemia (blood, chemically induced, pathology)
• Myocardium (pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Nitric Oxide (blood)
• Nitric Oxide Synthase (blood)
• Peptide Fragments (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Troponin I (metabolism)
• Urotensins (pharmacology)