Elevated resting arterial blood pressure (BP) and heart rate (HR) are both associated with poor life quality prognosis and shorter life span (Palatini 1999; Wang et al 2005; Verrier & Tan 2009; Courand & Lantelme, 2014). Aerobic metabolism plays an important role in the cardiac function. A ~50% reduction in citrate synthase (CS) activity in skeletal muscle of the A/J compared to C57BL/6J (B6) strain has been reported (Ratkevicius et al 2010). The reduction is associated with mutated Cs gene in A/J strain. The effect of this inherited reduction on the cardiovascular function has not been explored. Our hypothesis was that if the reduced CS activity leads to the metabolic challenges in the tissues, cardiovascular function might vary between the carriers of different Cs alleles. The aim of this study was to examine the effect of different levels in CS activity on cardiovascular function in mice. Physiological functions between inbred strains can vary because of extensive genetic differences. A congenic strain model confines the genetic differences to a restricted genomic region introgressed from a donor to the host strain. Our research model consisted of the B6 strain (host), congenic B6.A-(rs3676616-D10Utsw1)/Kjn (B6.A) and their hybrids (F1). The congenic strain is characterized by ~1.5-Mb region (contains the Cs gene) introgressed from a donor strain, A/J. A non-invasive tail-cuff setup (CODA, Kent Scientific, US) for systolic and diastolic BP and HR measurements was used during three consecutive days in 70-day old B6 (n=14), F1 (n=14) and B6.A (n=14) mice approximately equally divided between males and females. Animals were restrained but unsedated during the procedure which took 20 minutes and comprised 30 BP and HR recordings per animal. Systolic and diastolic BPs were averaged across 30 recordings, and HR was averaged over the 3 highest values. Presented values are means ± SD compared by 2-way ANOVA (group and sex). Neither HR nor BP differed between days. Therefore values were pooled for the analyses and are presented as an average across three days. There was no significant group effect (p>0.05) on either BP (systolic: 97.7 ± 8.8, 100.8 ± 13.0, and 96.8 ± 8.8 mmHg; diastolic: 67.6 ± 9.7, 72.0 ± 11.6 , and 67.1 ± 8.5 mmHg in B6, F1, and B6.A, respectively) or HR (544 ± 102, 543 ± 110, and 543 ± 107 bpm in B6, F1, and B6.A, respectively). Sex effect was detected on HR (females: 595 ± 76, males: 497 ± 104 bpm; p=0.001) but not BP. There was no strain by sex interaction observed in either BP or HR. Inherited lower CS activity does not affect cardiovascular function at rest in young adult mice. It suggests that a sufficient reserve of CS activity exists to maintain circulation unaltered, at least under the resting condition.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB019
Poster Communications: Reduction in citrate synthase activity does not affect arterial blood pressure or heart rate
T. Venckunas1, R. Zelniene1, I. Libnickiene1, A. Ratkevicius1,2, A. Lionikas2
1. Lithuanian Sports University, Kaunas, Lithuania. 2. University of Aberdeen, Aberdeen, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.