Ghrelin protects myocardium from isoproterenol-induced injury in rats

Acta Pharmacol Sin. 2004 Sep;25(9):1131-7.

Abstract

Aim: To investigate the cardiac protective effects of ghrelin in rat with myocardial injury induced by isoproterenol (ISO).

Methods: Rats were subcutaneously injected ISO 40 mg/kg/d with or without ghrelin 1 or 10 nmol/kg/d for 2 d. Hemodynamic parameters including mean arterial blood pressure and left ventricular pressure were measured at 12 h after the last injection with ISO and/or ghrelin. Plasma lactate dehydrogenase (LDH) activity, plasma and myocardial contents of malondialdehyde (MDA), and conjugated diene were measured. Plasma ghrelin and endothelin-1 levels were assayed using radioimmunoassay methods. Endothelin-1 and ghrelin mRNA were determined using RT-PCR.

Results: About 45 % (5/11) of rats after treatment with ISO alone died during experimental periods. However, no rats died after administration with ghrelin 10 nmol/kg/d (0/11, P<0.05). Ghrelin also obviously ameliorated the hemodynamic disturbance in rats induced by ISO. The plasma LDH activity, contents of myocardial and plasma MDA, and conjugated diene level in plasma in ISO+G10 nmol/kg/d group were decreased by 28 %, 34 %, 73 %, and 38 % compared with those of ISO group (all P<0.01) respectively. ISO-induced endothelin-1 mRNA over-expression was inhibited and endothelin-1 level in plasma were inhibited by ghrelin 1 and 10 nmol/kg/d. The ghrelin levels in plasma and ghrelin mRNA in myocardium were increased in the rats after injection of ISO. The plasma ghrelin level was further increased after ghrelin administration.

Conclusion: Ghrelin has a protective effect against ISO-induced myocardial injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Endothelin-1 / biosynthesis*
  • Endothelin-1 / blood
  • Endothelin-1 / genetics
  • Ghrelin
  • Isoproterenol
  • L-Lactate Dehydrogenase / blood
  • Male
  • Malondialdehyde / blood
  • Malondialdehyde / metabolism
  • Myocardial Ischemia / chemically induced
  • Myocardial Ischemia / metabolism*
  • Myocardium / metabolism
  • Peptide Hormones / biosynthesis
  • Peptide Hormones / genetics
  • Peptide Hormones / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cardiotonic Agents
  • Endothelin-1
  • Ghrelin
  • Peptide Hormones
  • RNA, Messenger
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Isoproterenol