Abstract 040: Evidence Of Increased Glycolysis In Renal Cortex Of High Salt Fed Sprague Dawley Rats

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To determine whole kidney O 2 and substance metabolism in an unanesthetized state, arterial (A), renal venous (Vr) blood and urine (U) were analyzed together with measurements of renal blood flow (RBF), blood pressure (BP) and GFR in conscious freely moving male SD rats. RBF and BP were measured continuously (24/7) via chronically implanted ultrasonic flow probe and A-line respectively. A and Vr blood through chronically implanted catheters and urine (U) were sampled intermittently when rats were fed a 0.4% NaCl (LS) diet and on days 7, 14, and 21 after switching to a 4.0% NaCl (HS) diet (HS7, HS14, HS21). A and Vr O 2 contents were determined by radiometer and a global metabolomic analysis was performed at the JAX Laboratory (LC-MS-MS). GFR was determined in another group of rats by transcutaneous detection of the attenuation of i.v. injected FITC sinistrin. Cortical (Cx) and outer medullary (OM) tissues were obtained from the other group of rats and underwent metabolomic and mRNAseq analyses (Novogene). From another group of rats, glomeruli (Glo), proximal tubules (PT) and non-PT were isolated for RT-PCR. BP and RBF slightly increased by HS3 (P<0.05) and were sustained at these levels. O 2 extraction rose progressively from 0.10 ± 0.01 at LS to 0.14 ± 0.01 at HS21 (P<0.05). GFR increased from 0.64 to 0.83 mL/min/100 g (P<0.05) at HS7 and sustained. Na + reabsorption and O 2 consumption were positively correlated. Clear distinctions were observed in a sparse partial least squares discriminant analysis of tissue metabolomics among LS, HS14, and HS21. The mRNAseq analysis found that the HS diet resulted in the activation of immune system-related genes in both Cx and OM and the downregulation of genes related to the TCA cycle and metabolism of amino acids and fatty acids in Cx only. In contrast, glycolysis-related genes including hexokinase ( Hk ) and pyruvate kinase ( Pkm ) were upregulated in Cx. Metabolic fluxes (A-Vr-U) showed the increased release of lactate and pyruvate from the kidney when fed HS. Increased mRNA expression of Hk and Pkm in HS21 was observed only in PT but not in Glo and non-PT. In summary, SD rats fed a HS diet underwent changes in RBF, O 2 extraction, and utilization of substrates with evidence of increased glycolysis.