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Status of β-Adrenoceptors, G-Proteins, and Adenylyl Cyclase in Ischemic Heart Disease

  • Naranjan S. Dhalla
  • Sujata Persad
  • Vincenzo Panagia
  • Sebu Mochizuki
  • Robert E. Beamish
Part of the Progress in Experimental Cardiology book series (PREC, volume 1)

Abstract

It is now well known that the positive inotropic responses of ischemia-reperfused hearts to adrenergic stimulation are markedly attenuated; however, the mechanisms for this abnormality are not fully understood. Earlier studies have revealed an increase, a decrease, or no change in the β-adrenoceptor-adenylyl cyclase system in ischemic-reperfused hearts, but such conflicting results appear to be due to differences in the experimental model, times of inducing ischemia as well as reperfusion, and the methods employed for studying biochemical parameters. Recent studies have revealed that the alterations in the β-adrenergic receptor mechanisms in the ischemic heart were different from those in ischemic-reperfused hearts. The major problem in the ischemic heart appears to result from uncoupling of β-adrenoceptors with adenylyl cyclase, whereas the problem in the ischemic-reperfused heart seems to be in the decrease of β-adrenoceptor numbers, depression in the catalytic site of adenylyl cyclase, and a decrease in Gs-protein function. Nonetheless, ischemia-reperfusion-induced changes in the β-adrenoceptors and adenylyl cyclase system have been demonstrated to be prevented by the presence of superoxide dismutase plus catalase, a combination which is known to remove the actions of H2O2. Since H2O2 and oxyradicals were found to produce biphasic changes in the β-adrenergic signal transduction mechanism, it is likely that the observed changes in the ischemic and ischemic-reperfused hearts may be due to the accumulation of low vs. high concentrations of oxyradicals and oxidants such as H2O2. On the basis of this evidence, it is suggested that an increase in oxidative stress during both the ischemic and reperfusion phases may play an important role in the alteration of β-adrenergic receptors, the adenylyl cyclase and Gs-protein system, and the attenuation of the inotropic responses of the ischemic-reperfused hearts to catecholamines.

Keywords

Adenylate Cyclase Xanthine Oxidase Adenylyl Cyclase Adrenergic Receptor Oxygen Free Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Naranjan S. Dhalla
    • 1
  • Sujata Persad
    • 1
  • Vincenzo Panagia
    • 1
  • Sebu Mochizuki
    • 2
  • Robert E. Beamish
    • 1
  1. 1.St. Boniface General Hospital Research CentreCanada
  2. 2.Jikei University School of MedicineJapan

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