Maternal Nutrient Restriction Alters Ca2+ Handling Properties and Contractile Function of Isolated Left Ventricle Bundles in Male But Not Female Juvenile Rats.

Thomas J Harvey,Janna L Morrison,Giuseppe S Posterino,Robyn M Murphy,Nick Ashton

doi:10.1371/journal.pone.0138388

Thomas J Harvey, Janna L Morrison + Show 3 more

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https://doi.org/10.1371/journal.pone.0138388

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Journal: PloS one	Publication Date: Sep 25, 2015
Citations: 19	License type: CC BY 4.0

Affiliation: La Trobe University, University of South Australia

Abstract

Intrauterine growth restriction (IUGR), defined as a birth weight below the 10th centile, may be caused by maternal undernutrition, with evidence that IUGR offspring have an increased risk of cardiovascular disease (CVD) in adulthood. Calcium ions (Ca2+) are an integral messenger for several steps associated with excitation-contraction coupling (ECC); the cascade of events from the initiation of an action potential at the surface membrane, to contraction of the cardiomyocyte. Any changes in Ca2+ storage and release from the sarcoplasmic reticulum (SR), or sensitivity of the contractile apparatus to Ca2+ may underlie the mechanism linking IUGR to an increased risk of CVD. This study aimed to explore the effects of maternal nutrient restriction on cardiac function, including Ca2+ handling by the SR and force development by the contractile apparatus. Juvenile Long Evans hooded rats born to Control (C) and nutrient restricted (NR) dams were anaesthetized for collection of the heart at 10–12 weeks of age. Left ventricular bundles from male NR offspring displayed increased maximum Ca2+-activated force, and decreased protein content of troponin I (cTnI) compared to C males. Furthermore, male NR offspring showed a reduction in rate of rise of the caffeine-induced Ca2+ force response and a decrease in the protein content of ryanodine receptor (RYR2). These physiological and biochemical findings observed in males were not evident in female offspring. These findings illustrate a sex-specific effect of maternal NR on cardiac development, and also highlight a possible mechanism for the development of hypertension and hypertrophy in male NR offspring.

Highlights

Intrauterine growth restriction (IUGR) is defined as a birth weight less than the 10th centile for gestational age [1]
We have examined the effects of maternal nutrient restricted (NR) on cardiac function in young male and female offspring
The novel findings of this study were that NR increased maximum Ca2+-activated force in only male offspring, and that this increase was associated with a reduction in the expression of content of troponin I (cTnI)

Summary

Introduction

Intrauterine growth restriction (IUGR) is defined as a birth weight less than the 10th centile for gestational age [1]. In an attempt to understand the basis of the increased risk of disease described above, several previous studies have examined the effects of IUGR on the contractility of the heart. These studies have predominately examined whole heart function from IUGR animals (e.g. left ventricular pressure and/or mean arterial pressure) which have typically found both increased ventricular pressure [10,11,12,13,14] and decreased stroke volume [15] implying changes to some step(s) within the Excitation-Contraction Coupling (ECC) cascade. At the end of the depolarization phase the SR rapidly re-accumulates Ca2+ via the SR Ca2+-ATPases (SERCA; of which the cardiac isoform, SERCA2a predominates) resulting in relaxation of the cardiomyocyte

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