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Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression

Department of Cardiothoracic Surgery, Alfred Hospital & Department of Surgery, Monash University, Melbourne, Australia

Lea M Durham Delbridge

Laboratory of Cardiac Phenomics, Department of Physiology, University of Melbourne, Melbourne, Australia

Thierry Pedrazzini

Department of Pharmacology, University of Lausanne, Lausanne, Switzerland

Franklin L Rosenfeldt

Department of Cardiothoracic Surgery, Alfred Hospital & Department of Surgery, Monash University, Melbourne, Australia

Salvatore Pepe

Department of Cardiothoracic Surgery, Alfred Hospital & Department of Surgery, Monash University, Melbourne, Australia, salvatore.pepe@ med.monash.edu.au, Department of Surgery, Central & Eastern Clinical School, Monash University, Commercial Road, Melbourne, Australia

Introduction. The endogenous opioid system has been reported to interact with both the cardiac sympathetic and renin-angiotensin systems in exerting a local regulatory action on the heart.The goal of this investigation was to examine how cardiac levels of enkephalin production are altered in the development of normotensive primary hypertrophy due to elevated intra-cardiac angiotensin II (Ang II) production.

Methods. Atrial and ventricular methionine-enkephalin (ME) levels were measured by quantitative radioimmunoassay in 14 and 28-week-old male transgenic mice (TG1306/1R) and control mice.The TG1306/1R exhibit cardiac specific Ang II overexpression and cardiac hypertrophy, but not hypertension.

Results. TG1306/1R mice had significantly higher heart/body weight ratios H (15—20%) than control littermates at both 14 (p=0.02) and 28 weeks (p=0.04). Relative to controls, ME content was significantly elevated (approximately twofold) in atria and ventricles in the older 28-week TG1306/1R mice only. A significant inverse correlation between heart size and ME level was observed for 28-week TG1306/1R only.

Conclusions. We have provided evidence that a marked elevation of myocardial enkephalin level is observed in the established (but not early) phase of cardiac hypertrophy associated with cardiac-specific Ang II-overexpression.This study identifies a potentially important relationship between two endogenous peptidergic signalling systems involved in the regulation of growth and function of the hypertrophic heart.

Key Words: angiotensin II • enkephalin • hypertrophy • mouse • opioid peptide

Journal of Renin-Angiotensin-Aldosterone System, Vol. 8, No. 4, 153-159 (2007)
DOI: 10.3317/jraas.2007.030


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