Cardiac dysfunction in aging conscious rats: Altered cardiac cytoskeletal proteins as a potential mechanism

Samuel C. Lieber, Hongyu Qiu, Li Chen, You Tang Shen, Chull Hong, William C. Hunter, Nadine Aubry, Stephen F. Vatner, Dorothy E. Vatner

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The objective of this study was to test the hypothesis that the mechanism mediating left ventricular (LV) dysfunction in the aging rat heart involves, in part, changes in cardiac cytoskeletal components. Our results show that there were no significant differences in heart rate, LV pressure, or LV diameter between conscious, instrumented young [5.9 ± 0.3 mo (n = 9)] and old rats [30.6 ± 0.1 mo (n = 10)]. However, the first derivative of LV pressure (LV dP/dt) was reduced (8,309 ± 790 vs. 11,106 ± 555 mmHg/s, P < 0.05) and isovolumic relaxation time (τ) was increased (8.7 ± 0.7 vs. 6.3 ± 0.6 ms, P < 0.05) in old vs. young rats, respectively. The differences in baseline LV function in young and old rats, which were modest, were accentuated after β-adrenergic receptor stimulation with dobutamine (20 μg/kg), which increased LV dP/dt by 170 ± 9% in young rats, significantly more (P < 0.05) than observed in old rats (115 ± 5%). Volume loading in anesthetized rats demonstrated significantly impaired LV compliance in old rats, as measured by the LV end-diastolic pressure and dimension relationship. In old rat hearts, there was a significant (P < 0.05) increase in the percentage of LV collagen (2.4 ± 0.2 vs. 1.3 ± 0.2%), α-tubulin (92%), and β-tubulin (2.3-fold), whereas intact desmin decreased by 51%. Thus the cardiomyopathy of aging in old, conscious rats may be due not only to increases in collagen but also to alterations in cytoskeletal proteins.

Original languageEnglish (US)
Pages (from-to)H860-H866
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number2
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • Aging cardiomyopathy
  • Left ventricular diastolic function
  • Left ventricular systolic function
  • Tubulin

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