Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development

Ye Chen-Izu, Ling Chen, Tamás Bányász, Stacey L. McCulle, Byron Norton, Steven M. Scharf, Anuj Agarwal, Abhijit Patwardhan, Leighton T Izu, C. William Balke

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. Previous studies show that hypertrophied and failing hearts display alterations in excitation-contraction (E-C) coupling. However, it is unclear whether remodeling of the E-C coupling system occurs before or after heart disease development. We hypothesized that hypertension might cause changes in the E-C coupling system that, in turn, induce hypertrophy. Here we tested this hypothesis by utilizing the progressive development of hypertensive heart disease in the spontaneously hypertensive rat (SHR) to identify a window period when SHR had just developed hypertension but had not yet developed hypertrophy. We found the following major changes in cardiac E-C coupling during this window period. 1) Using echocardiography and hemodynamics measurements, we found a decrease of left ventricular ejection fraction and cardiac output after the onset of hypertension. 2) Studies in isolated ventricular myocytes showed that myocardial contraction was also enhanced at the same time. 3) The action potential became prolonged. 4) The E-C coupling gain was increased. 5) The systolic Ca2+ transient was augmented. These data show that profound changes in E-C coupling already occur at the onset of hypertension and precede hypertrophy development. Prolonged action potential and increased E-C coupling gain synergistically increase the Ca2+ transient. Functionally, augmented Ca2+ transient causes enhancement of myocardial contraction that can partially compensate for the greater workload to maintain cardiac output. The increased Ca2+ signaling cascade as a molecular mechanism linking hypertension to cardiac hypertrophy development is also discussed.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

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Excitation Contraction Coupling
Muscle Cells
Hypertrophy
Hypertension
Myocardial Contraction
Cardiomegaly
Inbred SHR Rats
Cardiac Output
Action Potentials
Heart Diseases
Heart Failure
Workload
Stroke Volume
Echocardiography
Hemodynamics

Keywords

  • Action potential
  • Heart failure
  • L-type Ca channel
  • Rryanodine receptor

ASJC Scopus subject areas

  • Physiology

Cite this

Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development. / Chen-Izu, Ye; Chen, Ling; Bányász, Tamás; McCulle, Stacey L.; Norton, Byron; Scharf, Steven M.; Agarwal, Anuj; Patwardhan, Abhijit; Izu, Leighton T; Balke, C. William.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 6, 12.2007.

Research output: Contribution to journalArticle

Chen-Izu, Ye ; Chen, Ling ; Bányász, Tamás ; McCulle, Stacey L. ; Norton, Byron ; Scharf, Steven M. ; Agarwal, Anuj ; Patwardhan, Abhijit ; Izu, Leighton T ; Balke, C. William. / Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 6.
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