Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension

Author:

Tran Kenneth1ORCID,Han June-Chiew1,Taberner Andrew J.12,Barrett Carolyn J.2,Crampin Edmund J.345,Loiselle Denis S.16

Affiliation:

1. Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand;

2. Department of Engineering Science, University of Auckland, Auckland, New Zealand;

3. Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Victoria, Australia;

4. School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia; and

5. School of Medicine, University of Melbourne, Parkville, Victoria, Australia

6. Department of Physiology, University of Auckland, Auckland, New Zealand;

Abstract

Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13BN) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS-13BN rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13BN groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy.

Funder

Virtual Physiological Rat Center funded through the NIH

National Heart Foundation of New Zealand

Royal Society of New Zealand Marsden Fast-Start

Royal Society of New Zealand Marsden Fund

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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