HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/H3301    most recent 00259.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen-Izu, Y. Articles by Balke, C. W. Search for Related Content PubMed PubMed Citation Articles by Chen-Izu, Y. Articles by Balke, C. W.

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

¹Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky; ²Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; ³Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary; and ⁴Center for Biomedical Engineering, University of Kentucky and ⁵Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky

Submitted 2 March 2007 ; accepted in final form 11 September 2007

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.

heart failure; action potential; L-type Ca²⁺ channel; ryanodine receptor