Cardiomegaly induced by pressure overload in newborn rats is accompanied by altered expression of the long isoform of G(s)alpha protein and deranged signaling of adenylyl cyclase

Mol Cell Biochem. 2003 Mar;245(1-2):157-66. doi: 10.1023/a:1022828430565.

Abstract

G proteins-coupled signaling pathways appear to play a role in the development of cardiac hypertrophy and its progression to heart failure. The present study aimed to investigate trimeric G proteins and adenylyl cyclase signaling in immature as well as in adult rat myocardium during this process caused by pressure overload. Pressure overload was induced in newborn (2-day-old) rats by abdominal aortic banding and myocardial preparations from left ventricular myocardium of immature (10-day-old) and adult (90-day-old) animals were analyzed for the relative content of different G protein subunits and adenylyl cyclase (AC) by immunoblotting with specific antibodies. A functional status of the AC signaling system was also evaluated. Normal maturation of rat heart was accompanied by increased expression of AC type V/VI and VII and of the long isoform (G(s)alphaL) of G(s)alpha protein. In parallel, the amounts of myocardial G(i)alpha/G(o)alpha proteins tended to decrease, and G(q)alpha/G(11)alpha and Gbeta did not change. Interestingly, whereas fluoride-stimulated AC activity increased in the course of maturation, activity of AC measured under other experimental conditions (stimulation by Mn2+, forskolin or isoproterenol) was lower in adult than in young rat myocardium. Pressure overload did not influence distribution of G proteins in immature myocardium, but considerably decreased the content of G(s)alphaL and increased G(o)alpha proteins in hearts of 90-day-old rats. These hearts exhibited worsened functional reserve as compared to age-matched controls and activity of AC was also markedly lower. A considerable reduction in Mn(2+)-stimulated AC activity together with similar decrease in AC activity determined under other stimulation conditions suggests that it is a function of AC catalytic subunit that is primarily impaired in this model of pressure overload.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Aging
  • Animals
  • Animals, Newborn*
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Cardiotonic Agents / pharmacology
  • Colforsin / pharmacology
  • Fluorides / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Gene Expression
  • Hypertrophy, Left Ventricular / metabolism
  • Isoproterenol / pharmacology
  • Manganese / pharmacology
  • Myocardium / metabolism
  • Pressure*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction

Substances

  • Cardiotonic Agents
  • Protein Isoforms
  • Colforsin
  • Manganese
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Isoproterenol
  • Fluorides