Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia

J Clin Invest. 1993 Dec;92(6):2644-52. doi: 10.1172/JCI116880.


Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. The ischemic bed showed a reduction in myocardial beta AR number (P < 0.005). Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds. Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Base Sequence
  • Cell Membrane / metabolism
  • Coronary Circulation
  • DNA Primers
  • DNA, Complementary / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • GTP-Binding Proteins / biosynthesis*
  • GTP-Binding Proteins / metabolism
  • Heart / physiology
  • Heart / physiopathology*
  • Immunoblotting
  • Isoproterenol / pharmacology
  • Kinetics
  • Molecular Sequence Data
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / physiopathology*
  • Myocardium / metabolism*
  • Physical Exertion
  • Polymerase Chain Reaction
  • Radioligand Assay
  • Receptors, Adrenergic, beta / biosynthesis*
  • Receptors, Adrenergic, beta / metabolism
  • Recombinant Fusion Proteins / biosynthesis
  • Swine
  • Swine, Miniature


  • DNA Primers
  • DNA, Complementary
  • Receptors, Adrenergic, beta
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Isoproterenol