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1 Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
2 Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada
3 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA
4 Department of Nutrition, University of Montreal, Montreal, Quebec, Canada; Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: christine.des.rosiers{at}umontreal.ca.
The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted utilization of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA, octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones, and subjected to an adrenergic stimulation (epinephrine 10 µM). 13C-labeled substrates were used to assess substrate selection for energy production. Compared to control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by (i) a smaller increase in contractility and developed pressure, (ii)a faster decline in the aortic flow, and (iii) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 ± 118 vs 825 ± 44 mU.min-1, p<0.01). At the metabolic level, SHR hearts presented: (i) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 ± 1 vs 44 ± 4 %, p<0.001) and an enhanced contribution of endogenous substrates (20 ± 4 vs 1 ± 4 %, p<0.01), and (ii) an increased lactate production from glycolysis, with a greater lactate to pyruvate production ratio. The addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 ± 155 vs 1,890 ± 89 mU.min-1, p<0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 ± 1.3 vs 15.8 ± 0.8 %, p<0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 ± 1.5 vs 19.0 ± 1.2 %, p<0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy production by MCFA supplementation.
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