title: Maternal Nutrient Restriction Alters Ca2+ Handling Properties and Contractile Function of Isolated Left Ventricle Bundles in Male But Not Female Juvenile Rats.
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.
authors.affiliation: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Vic, Australia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Harvey
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Vic, Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Murphy
authors.affiliation: School of Pharmacy and Medical Science, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.affiliation: Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Vic, Australia.
authors.forename: Giuseppe S
authors.initials: GS
authors.lastname: Posterino
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac; D051381:Rats; D020318:Rats, Long-Evans; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium