Morphologic, molecular and hemodynamic cardiac alterations in a model of nephropathy induced by puromycin aminonucleoside.

ABSTRACT

INTRODUCTION: Proteinuria and decreased glomerular filtration rate are assuming increased importance in defining cardiovascular risk in chronic renal insufficiency. The aim of this work was to study morphologic, molecular and hemodynamic cardiac alterations in an animal model of proteinuria and renal insufficiency induced by puromycin aminonucleoside (PAN). METHODS: Normotensive rats (n = 14) were injected with PAN (150 mg/kg, i.p.) or with vehicle. Blood pressure was measured daily and the animals were placed in metabolic cages for evaluation of urinary excretion of sodium, protein and creatinine. Fourteen days after PAN administration left ventricular hemodynamics were evaluated through a pressure tip micromanometer and heart morphology was examined. Transmural samples of left ventricle were then taken for mRNA quantification of SERCA2a, phospholamban (PLB), insulin-like growth factor 1 (IGF-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: The animals treated with PAN presented a decrease in creatinine clearance (14th day 2.24 +/- 0.32 vs. 4.51 +/- 1.08 ml/min) and an increase in proteinuria (14th day 51.0 +/- 9.0 vs. 3.8 +/- 0.7 mg/mg creatinine), without changes in systolic (14th day 151 +/- 7 vs. 141 +/- 6 mmHg) or diastolic blood pressure (14th day 85 +/- 7 vs. 86 +/- 3 mmHg), These alterations were accompanied by cardiac atrophy with decreased left ventricular contractility. A reduction in the SERCA2a/PLB mRNA ratio was observed without significant alteration in the expression of IGF-1 in the left ventricle. CONCLUSIONS: PAN-induced nephropathy is accompanied by cardiac atrophy, left ventricular dysfunction and alterations in the expression of genes involved in myocardial calcium kinetics. These findings were not accompanied by increases in blood pressure and may contribute to our understanding of the increased cardiovascular risk in chronic renal insufficiency.