Abstract 354: Mitochondrial Hyper-function in Renal Proximal Tubule Cells from Young Spontaneously Hypertensive Rats

Abstract

Recent evidence suggests that mitochondria play roles in the pathogenesis of hypertension. However, it is not clear whether mitochondrial dysfunction precedes or follows the development of hypertension. We hypothesize that mitochondrial bioenergetics is altered in renal proximal tubule (RPT) cells from spontaneously hypertensive rats (SHRs) and this alteration may occur prior to the development of sustained hypertension. Using immortalized RPT cells from 4-8 week old normotensive Wistar-Kyoto (WKY) and SHRs, we measured oxygen consumption rate (OCR) and compared the parameters of cellular bioenergetic in these RPT cells. Basal OCR was significantly higher in RPT cells from SHRs than WKY rats (245.5±31.9 vs. 154.4±43.7 pmol/min per 20,000 cells, mean±SD, P<0.001);the ATP synthesis-coupled OCR (65.9±3.3% vs. 55.0±6.6%, of basal OCR, P<0.001), maximum respiration (609.0±120.4 vs. 215.7±65.5 pmol/min per 20,000 cells, P<0.001) and reserve respiration (147.8±39.0% vs, 40.0±15.4% of basal OCR P<0.001) were also significantly higher in RPT cells from SHRs than WKY rats. In contrast, proton leak-linked OCR (15.4±3.6% vs. 19.2±5.9% of basal OCR, P<0.05) was lower in RPT cells from SHRs than WKY rats, and non-mitochondrial OCRs were similar (45.2±7.0 vs. 41.3±19.8 pmol/min per 20,000 cells, P>0.05). In support of these observations, adenosine triphosphate (ATP) levels were significantly higher in RPT cells from SHRs than WKY rats. Taken together, the observed bioenergetic alterations may contribute to the early mitochondrial dysfunction in RPT cells from SHRs prior to the onset of sustained hypertension.