Abstract

Our previous proteomic study revealed substantial differences in several proteins between Dahl salt-sensitive (SS) rats and salt-insensitive consomic SS.13BN rats. Subsequent studies indicated a role of fumarase insufficiency in the development of hypertension in SS rats. A global metabolic profiling study using gas chromatography/mass spectrometry (GC/MS) was performed in plasma of SS rats (n=9) and SS.13BN rats (n=8) on a 0.4% NaCl diet to gain further insights into the relationship between alterations in cellular intermediary metabolism and predisposition to hypertension. Principal component analysis of the data revealed a clear clustering and separation of metabolic profiles between SS rats and SS.13BN rats. 23 differential metabolites were identified (P<0.05). Levels of five TCA cycle-related metabolites, fumarate, cis-aconitate, isocitrate, citrate and succinate, were higher in SS rats. Pyruvate, which connects TCA cycle and glycolysis, was also increased in SS rats. Moreover, enzymatic activities of fumarase, aconitase, α-ketoglutarate dehydrogenase and succinyl-CoA synthetase were lower in the heart, liver or skeletal muscles of SS rats. The distinct metabolic features in SS and SS.13BN rats supports a role of abnormal TCA cycle in predisposing SS rats to developing salt-sensitive hypertension.

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