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Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.

Publication ,  Journal Article
Spinale, FG; Tempel, GE; Mukherjee, R; Eble, DM; Brown, R; Vacchiano, CA; Zile, MR
Published in: Cardiovascular research
August 1994

The aim was to examine the relationship between changes in myocyte function to changes in protein and mRNA content of components of the beta adrenergic system with tachycardia induced cardiomyopathy.Contractile function and beta adrenergic responsiveness were measured in isolated myocytes from control pigs (n = 6) and in pigs subjected to three weeks of pacing induced supraventricular tachycardia (n = 6). beta Receptor density and affinity, the relative content of the stimulatory (Gs) and inhibitory (Gi) subunits of the G protein complex, and adenylate cyclase activity were determined from sarcolemmal preparations. In order to determine whether these changes were accompanied by alterations in steady state mRNA levels for specific components of the beta adrenergic system, mRNA content for the beta 1 adrenergic receptor and the G alpha s and G alpha i2 subunits of the G protein complex was measured.Chronic supraventricular tachycardia caused a 36% increase in left ventricular end diastolic dimension and a 61% decrease in left ventricular fractional shortening compared to controls. The velocity of isolated myocyte shortening was 50% lower in myocytes from hearts with tachycardia cardiomyopathy than in control myocytes. In the presence of 50 nM isoprenaline or 2 microM forskolin, the velocity of myocyte shortening was 65% lower in the myopathic myocytes than in the controls. With the development of tachycardic cardiomyopathy, beta adrenergic receptor density fell by 25% with no change in affinity, Gs decreased by 35%, and Gi increased by over 50% compared to controls. Basal adenylate cyclase activity and isoprenaline and forskolin stimulated adenylate cyclase activity fell by over 50% with supraventricular tachycardia compared to controls. The relative content of G alpha i2 mRNA increased threefold with the development of tachycardic cardiomyopathy with no change in the relative abundance of mRNA for the beta 1 receptor or G alpha s when compared with controls.The changes in myocyte beta adrenergic responsiveness with the development of tachycardic cardiomyopathy are due to alterations in cellular mechanisms (decreased beta receptor and Gs density, increased Gi) and in molecular mechanisms (increased Gi mRNA content).

Duke Scholars

Published In

Cardiovascular research

DOI

EISSN

1755-3245

ISSN

0008-6363

Publication Date

August 1994

Volume

28

Issue

8

Start / End Page

1243 / 1250

Related Subject Headings

  • Tachycardia, Supraventricular
  • Swine
  • Receptors, Adrenergic, beta
  • Myocardium
  • Isoproterenol
  • GTP-Binding Proteins
  • Colforsin
  • Cell Size
  • Cardiovascular System & Hematology
  • Cardiomyopathies
 

Citation

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Chicago
ICMJE
MLA
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Spinale, F. G., Tempel, G. E., Mukherjee, R., Eble, D. M., Brown, R., Vacchiano, C. A., & Zile, M. R. (1994). Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia. Cardiovascular Research, 28(8), 1243–1250. https://doi.org/10.1093/cvr/28.8.1243
Spinale, F. G., G. E. Tempel, R. Mukherjee, D. M. Eble, R. Brown, C. A. Vacchiano, and M. R. Zile. “Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.Cardiovascular Research 28, no. 8 (August 1994): 1243–50. https://doi.org/10.1093/cvr/28.8.1243.
Spinale FG, Tempel GE, Mukherjee R, Eble DM, Brown R, Vacchiano CA, et al. Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia. Cardiovascular research. 1994 Aug;28(8):1243–50.
Spinale, F. G., et al. “Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.Cardiovascular Research, vol. 28, no. 8, Aug. 1994, pp. 1243–50. Epmc, doi:10.1093/cvr/28.8.1243.
Spinale FG, Tempel GE, Mukherjee R, Eble DM, Brown R, Vacchiano CA, Zile MR. Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia. Cardiovascular research. 1994 Aug;28(8):1243–1250.
Journal cover image

Published In

Cardiovascular research

DOI

EISSN

1755-3245

ISSN

0008-6363

Publication Date

August 1994

Volume

28

Issue

8

Start / End Page

1243 / 1250

Related Subject Headings

  • Tachycardia, Supraventricular
  • Swine
  • Receptors, Adrenergic, beta
  • Myocardium
  • Isoproterenol
  • GTP-Binding Proteins
  • Colforsin
  • Cell Size
  • Cardiovascular System & Hematology
  • Cardiomyopathies