Abstract 624: Chronic High Fat Diet Increases Sodium Reabsorption and αENaC Expression Prior to the Onset of Hypertension in Dahl Salt-Sensitive Rats
An increase in distal nephron-dependent sodium (Na+) reabsorption plays a primary role in the development of obesity-induced hypertension. However, the specific Na+ transporter involved in this process is unknown. The present studies were undertaken to determine the role of the epithelial Na+ channel (ENaC) in the development of high fat-diet (HFD)-induced hypertension. Given that human obesity-induced hypertension is largely salt-sensitive, we chose to expose Dahl salt-sensitive (DSS) rats to either a chronic HFD (42% kcal from fat, normal salt, 0.25%, N=7)) or standard diet (STD, 10% kcal from fat, normal salt, 0.25%, N=7), measure blood pressures (BP) telemetrically, and collect 24 hr urine for Na+ each week, for 4 weeks. In a separate group of DSS rats, we isolated cortical collecting ducts for determination of αENaC protein expression at baseline, 1 week, and 4 weeks following STD or HFD. Telemetric systolic blood pressure (SBP) values increased significantly (P<0.05) from a baseline value of 118±2.7 mmHg to 135±4.4 mmHg after just 2 weeks on the HFD, and to 146.9±2.6 mmHg after 4 weeks (P<0.01). SBPs did not change in DSS rats on STD for the entire 4 weeks. Prior to the increase in BP, 24 hr urine Na+ excretion significantly decreased in DSS rats on HFD compared to STD (0.94±0.15 μmol/min vs. 1.35±0.09, P<0.05). Furthermore, compared to baseline, αENaC protein levels significantly increased after 1 week of HFD [0.93±0.13 and 0.51±0.02 densitometric units (DU) respectively, P<0.01], but not after 1 week of STD (0.46±0.02 DU). Following 4 weeks of HFD, αENaC protein levels remained significantly elevated (0.66±0.05 DU; P<0.05) compared to baseline. These results suggest that increased cortical collecting duct αENaC protein expression may contribute to the reduction in Na+ excretion that initiates the hypertensive cascade in HFD-induced hypertension.
- © 2012 by American Heart Association, Inc.