Isoproterenol Induces in Vivo Functional and Metabolic Abnormalities: Similar to Those Found in the Infarcted Rat Heart

J Physiol Pharmacol. 2009 Sep;60(3):31-9.

Abstract

Chronic isoproterenol administration produces a rapid, highly reproducible rodent model of cardiac hypertrophy. Yet, despite widespread use of this model, the effects of isoproterenol on in vivo cardiac function and substrate metabolism are unknown. Isoproterenol (5 mg.kg(-1).day(-1)) was infused for 7 days in male Wistar rats (n = 22). In vivo magnetic resonance imaging (MRI) showed that left ventricular mass increased by 37% and end-diastolic and systolic volumes increased by 33% and 73%, respectively, following isoproterenol infusion. Cardiac function at the base of the left ventricle was normal, but apical ejection fraction decreased from 90% to 31% and apical free wall thickening decreased by 94%, accompanied by increased fibrosis and inflammation. Myocardial palmitate oxidation rates were 25% lower, and citrate synthase and medium chain acyl-coenzyme A dehydrogenase activities were reduced by 25% and 29%, respectively, following isoproterenol infusion. Fatty acid transporter protein levels were 11-52% lower and triglyceride concentrations were 55% lower in isoproterenol-infused rat hearts. Basal glycolysis and glycogen concentration were not changed, yet insulin stimulated glycolysis was decreased by 32%, accompanied by 33% lower insulin stimulated glucose transporter, GLUT4, protein levels in rat hearts following isoproterenol infusion, compared with controls. In conclusion, isoproterenol infusion impaired in vivo cardiac function, induced hypertrophy, and decreased both fatty acid and glucose metabolism, changes similar in direction and magnitude to those found in the rat heart following moderate severity myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / toxicity*
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Disease Models, Animal*
  • Fatty Acid Transport Proteins / metabolism
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Heart Ventricles / drug effects
  • Heart Ventricles / enzymology
  • Heart Ventricles / metabolism*
  • Heart Ventricles / pathology
  • Hypertrophy, Left Ventricular / chemically induced*
  • Hypertrophy, Left Ventricular / complications
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • Isoproterenol / toxicity*
  • Magnetic Resonance Imaging, Cine
  • Male
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / complications
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Perfusion
  • Rats
  • Rats, Wistar
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology

Substances

  • Adrenergic beta-Agonists
  • Fatty Acid Transport Proteins
  • Fatty Acids
  • Glucose Transporter Type 4
  • Slc2a4 protein, rat
  • Glucose
  • Isoproterenol