Abstract 16455: Increased Renal Proximal Tubule Bioenergetic Activity Prior to the Onset Ofsustained Hypertension in Spontaneously Hypertensive Rats
Essential hypertension is associated with increased sodium transport by the renal proximal tubule. Renal proximal tubule cells from spontaneously hypertensive rats (SHR) have higher oxygen consumption than cells from normotensive Wistar-Kyoto rats (WKY). Pyruvate dehydrogenase complex (PDC) is critical in linking glycolysis and oxidative phosphorylation. We tested the novel hypothesis that increased PDC activity is associated with a hypertensive phenotype. Using both immortalized and primary cultured renal proximal tubule cells from 4-8 week old WKY and SHR, we found that renal proximal tubule cells from SHR, compared to WKY, had higher basal and ATP synthesis-linked oxygen consumption rate, maximum respiration, and reserve respiration. These bioenergetic parameters indicated increased mitochondrial function in renal proximal tubule cells from SHR. Consistently, PDC activity was higher in renal proximal tubule cells (4.21±1.0 vs. 1.81±0.4 ΔmOD450 nm/min/mg protein, P<0.05) and renal cortical homogenates (14.28±2.1 vs. 9.91±1.2 ΔmOD450 nm/min/mg protein, P<0.01) from SHR compared to WKY. We next examined the effect of dichloroacetate (DCA), an inhibitor of PDC kinase which increases PDC activity. We found that DCA treatment for 6 days increased systolic blood pressure in both 3-week old SHR (vehicle 112.5±2.9 mmHg vs. DCA 126.8±4.0 mmHg, p<0.05) and WKY rats (vehicle 101.2±3.1 mmHg vs. DCA 113.6±2.8 mmHg, P<0.05). Taken together, these data support the hypothesis that mitochondrial function is increased in renal proximal tubule cells from SHR compared to WKY and the increased PDC function may contribute to the pathogenesis of hypertension.
- © 2013 by American Heart Association, Inc.