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J Cardiovasc Pharmacol Ther ; 17(4): 412-6, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22626958

ABSTRACT

Cardiovascular disease (CVD) remains one of the most common causes of morbidity and mortality in patients with chronic renal disease. It has been recently postulated that the loss or reduced levels of renalase in patients with chronic renal disease are, at least in part, responsible for elevated plasma catecholamine levels, which leads to increased CVD. Therefore, the aim of the present study was to evaluate whether renalase administration might serve as a therapeutic drug, decreasing the severity of CVD in 5/6 nephrectomized (Nx) rats. The current study was conducted on 30 male Wistar albino rats divided into the following groups: group I: sham-operated rats that received phosphate-buffered saline (PBS) subcutaneously (s.c.) for 4 weeks following sham operation, group II: rats in which 5/6 Nx was done and then the rats received PBS daily s.c. for 4 weeks following 5/6 Nx, and group III: rats in which 5/6 Nx was done and then the rats received recombinant renalase daily s.c. for 4 weeks following 5/6 Nx. 5/6 nephrectomy resulted in a significant increase in mean arterial pressure, left ventricular (LV)/body weight ratio, LV hydroxyproline concentration, plasma creatinine, blood urea nitrogen (BUN), and noradrenaline (NA) levels as well as significant decrease in LV papillary muscle developed tension in group II compared with the sham-operated group I. Administration of renalase to group III resulted in significant amelioration of all studied parameters with the exception of plasma creatinine and BUN which were not significantly different from nontreated group II. The results of the current study identify renalase as a new therapeutic modality that might modulate cardiac function and systemic blood pressure in renalase-deficient states like chronic renal disease.


Subject(s)
Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Disease Models, Animal , Enzyme Replacement Therapy , Monoamine Oxidase/therapeutic use , Renal Insufficiency, Chronic/physiopathology , Animals , Cardiotonic Agents/administration & dosage , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Cardiovascular Diseases/physiopathology , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Hypertension/etiology , Hypertension/pathology , Hypertension/physiopathology , Hypertension/prevention & control , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Injections, Subcutaneous , Male , Monoamine Oxidase/administration & dosage , Monoamine Oxidase/deficiency , Monoamine Oxidase/genetics , Nephrectomy/adverse effects , Papillary Muscles/drug effects , Papillary Muscles/pathology , Papillary Muscles/physiopathology , Random Allocation , Rats , Rats, Wistar , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Severity of Illness Index , Sus scrofa
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