Valsartan Attenuates Cardiac and Renal Hypertrophy in Rats With Experimental Cardiorenal Syndrome Possibly Through Down-Regulating galectin-3 Signaling

Eur Rev Med Pharmacol Sci. 2016;20(2):345-54.

Abstract

Objective: Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model.

Materials and methods: Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal.

Results: Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment.

Conclusions: Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

MeSH terms

  • Animals
  • Cardio-Renal Syndrome / drug therapy*
  • Cardiomegaly / pathology
  • Disease Models, Animal
  • Down-Regulation
  • Echocardiography
  • Galectin 3 / metabolism*
  • Glomerular Filtration Rate
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Failure / physiopathology
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Valsartan / pharmacology*

Substances

  • Galectin 3
  • Valsartan