Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats

Y.H. Looi, K.A. Kane, A.R. McPhaden, C.L. Wainwright

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

1The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite.2In sham-operated rats, the effects of in vivo administration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP), ex vivo leukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.3In pentobarbitone-anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.; n=19) or saline (n=18) given 5 min pre-occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavenger N-mercaptopropionyl-glycine (MPG) (20 mg kg−1 h−1) before AM.4AM treatment significantly reduced mean arterial blood pressure (MABP) and increased ex vivo chemiluminescence (CL) generation from leukocytes in sham-operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.5AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74; P<0.05) and the incidences of ventricular fibrillation (from 61 to 26%; P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM-induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.6This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.
LanguageEnglish
Pages599-609
Number of pages10
JournalBritish Journal of Pharmacology
Volume148
DOIs
Publication statusPublished - 2006

Fingerprint

Adrenomedullin
Peroxynitrous Acid
Myocardial Ischemia
Cardiac Arrhythmias
Nitric Oxide
Arterial Pressure
Nitric Oxide Synthase
Leukocytes
Ventricular Premature Complexes
Incidence
Ventricular Fibrillation
Pentobarbital
Luminescence
Glycine
Endothelium
Ligation
Arginine
Reactive Oxygen Species
Coronary Vessels
Ischemia

Keywords

  • cardioprotection
  • ventricular arrhythmias
  • leukocytes
  • ischaemia
  • anaesthetized rats
  • adrenomedullin

Cite this

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abstract = "1The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite.2In sham-operated rats, the effects of in vivo administration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP), ex vivo leukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.3In pentobarbitone-anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.; n=19) or saline (n=18) given 5 min pre-occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavenger N-mercaptopropionyl-glycine (MPG) (20 mg kg−1 h−1) before AM.4AM treatment significantly reduced mean arterial blood pressure (MABP) and increased ex vivo chemiluminescence (CL) generation from leukocytes in sham-operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.5AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74; P<0.05) and the incidences of ventricular fibrillation (from 61 to 26{\%}; P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM-induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.6This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.",
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author = "Y.H. Looi and K.A. Kane and A.R. McPhaden and C.L. Wainwright",
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Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats. / Looi, Y.H.; Kane, K.A.; McPhaden, A.R.; Wainwright, C.L.

In: British Journal of Pharmacology, Vol. 148, 2006, p. 599-609.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats

AU - Looi, Y.H.

AU - Kane, K.A.

AU - McPhaden, A.R.

AU - Wainwright, C.L.

PY - 2006

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N2 - 1The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite.2In sham-operated rats, the effects of in vivo administration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP), ex vivo leukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.3In pentobarbitone-anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.; n=19) or saline (n=18) given 5 min pre-occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavenger N-mercaptopropionyl-glycine (MPG) (20 mg kg−1 h−1) before AM.4AM treatment significantly reduced mean arterial blood pressure (MABP) and increased ex vivo chemiluminescence (CL) generation from leukocytes in sham-operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.5AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74; P<0.05) and the incidences of ventricular fibrillation (from 61 to 26%; P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM-induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.6This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.

AB - 1The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)-induced arrhythmias via nitric oxide (NO) and peroxynitrite.2In sham-operated rats, the effects of in vivo administration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP), ex vivo leukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.3In pentobarbitone-anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.; n=19) or saline (n=18) given 5 min pre-occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavenger N-mercaptopropionyl-glycine (MPG) (20 mg kg−1 h−1) before AM.4AM treatment significantly reduced mean arterial blood pressure (MABP) and increased ex vivo chemiluminescence (CL) generation from leukocytes in sham-operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.5AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74; P<0.05) and the incidences of ventricular fibrillation (from 61 to 26%; P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM-induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.6This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.

KW - cardioprotection

KW - ventricular arrhythmias

KW - leukocytes

KW - ischaemia

KW - anaesthetized rats

KW - adrenomedullin

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U2 - 10.1038/sj.bjp.0706771

DO - 10.1038/sj.bjp.0706771

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