Spontaneously Hypertensive Rat (SHR) Display Alterations in Carbohydrate Metabolism And Function At An Early Age

Abstract

The SHR, a genetic model of hypertension with a CD36 gene defect, develops left ventricular hypertrophy (LVH) between 9 and 12 weeks of age. We reported that 15‐wk‐old SHR display a reduced exogenous fatty acid (FA) oxidation, while that of carbohydrate (CHO) was unchanged despite an enhanced glycolysis. This study aimed at clarifying whether these alterations are characteristic of this rat strain or result from metabolic gene remodeling linked to LVH. We assessed the metabolic and functional profile of working hearts perfused with 13C‐labeled substrates at 7 weeks (SHR vs Wistar), and cardiac metabolic gene expression by qPCR at 7 and 15 weeks. As young Wistar hearts were not able to maintain stable cardiac output at 80 mmHg, they were perfused at 70 mmHg afterload to match functions with SHR. At the metabolic level, SHR hearts displayed a 40% lower FA β‐oxidation, while CHO oxidation was increased by 50% (p<0.05). qPCR data revealed that SHR hearts showed marginal differences in mRNA levels for genes involved in FA and CHO metabolism at 7 weeks, but a significant increase in all these gene transcripts at 15 weeks. Compared to their 15‐week‐old counterpart, young SHR hearts displayed a similar lower FA oxidation, but an increase in CHO oxidation. The latter difference appears to be explained by transcriptional changes in PDK4 linked to LVH, and may confer to young SHR hearts the capacity to withstand a higher workload.(Supported by the Fondation Bettencourt Schueller and CIHR).