Atrial natriuretic peptide protects against ischemia-reperfusion injury in the isolated rat heart

Kenji Sangawa, Koji Nakanishi, Kozo Ishino, Masahiro Inoue, Masaaki Kawada, Shunji Sano

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Background. Atrial natriuretic peptide (ANP), a stimulator of particulate guanylate cyclase, has been found to protect against reoxygenation-induced hypercontracture in isolated cardiomyocytes by increasing cyclic guanosine monophosphate synthesis. The purpose of this study was to investigate the cardioprotective effects of ANP against ischemia-reperfusion injury in isolated rat hearts. Methods. Twenty-four hearts were perfused with ANP at 0.01, 0.1, and 1 μmol/L or without ANP (n = 6 each) in normoxic conditions. Because 0.1 μmol/L ANP induced a threefold increase in cyclic guanosine monophosphate release into the coronary effluent without any effect on cardiac function, we used the 0.1 μmol/L ANP dose for ischemia-reperfusion studies. Eighteen hearts were subjected to 15 minutes of normothermic global ischemia followed by 15 minutes of reperfusion. The hearts were divided into three groups (n = 6 each). In group 1, ANP was added before ischemia. In group 2, ANP was added to the reperfusate. Hearts were untreated in the control group. Results. In group 1, the postischemic recovery of cardiac output, coronary flow, and cyclic guanosine monophosphate release was similar to the control group. In group 2, the recovery of cardiac output was significantly better than the control group (82.1% ± 9.8% vs 61.8% ± 6.8%, respectively, p < 0.01) with a similar trend to recovery of coronary flow (90.7% ± 8.5% vs 79.3% ± 11.8%, respectively). The improved cardiac function was closely related to a significant increase in postischemic cyclic guanosine monophosphate release. Conclusions. Administration of ANP at the time of reperfusion protects the myocardium from ischemia-reperfusion injury. The concentrations of administration must not only increase the release of cyclic guanosine monophosphate release, but also lack negative inotropic effects.

Original languageEnglish
Pages (from-to)233-237
Number of pages5
JournalAnnals of Thoracic Surgery
Issue number1
Publication statusPublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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