Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol

Am J Physiol. 1999 May;276(5):H1678-90. doi: 10.1152/ajpheart.1999.276.5.H1678.

Abstract

Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta1-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenylyl Cyclases / metabolism
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Calcium-Transporting ATPases / metabolism
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / mortality
  • Cardiomyopathy, Dilated / pathology
  • Carteolol / pharmacology*
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Follow-Up Studies
  • Furazolidone / pharmacology
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / pathology*
  • Heart Rate / drug effects
  • Monoamine Oxidase Inhibitors / pharmacology
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / enzymology
  • Myocardium / chemistry
  • Myocardium / cytology
  • Myocardium / enzymology
  • Myofibrils / chemistry
  • Myofibrils / enzymology
  • Receptors, Adrenergic, beta / physiology
  • Sarcoplasmic Reticulum / chemistry
  • Sarcoplasmic Reticulum / enzymology
  • Survival Analysis
  • Turkey
  • Ventricular Function, Left

Substances

  • Adrenergic beta-Antagonists
  • Monoamine Oxidase Inhibitors
  • Receptors, Adrenergic, beta
  • Furazolidone
  • Adenosine Triphosphate
  • Carteolol
  • Adenylyl Cyclases
  • Calcium-Transporting ATPases