Abstract 18173: Novel Function of CFTR in High Salt- and Fructose-induced Hypertension
Background: The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporters and encodes a cAMP- PKA-activated Cl- channel in the vascular smooth muscle cells (VSMCs). Recent study indicates a potential role of CFTR in the regulation of vascular functions and in the high fructose-salt-induced hypertension. In this study we will test our hypothesis that activation of CFTR may be a novel and important mechanism for the high salt- and fructose-induced hypertension.
Methods: The HD-X11 transmitters for telemetry recordings of both blood pressure and ECG (Data Science International) were implanted into CFTR-knockout (CFTR-/-) mice (8-week old, male) and their age- and gender-matched wild-type (CFTR+/+) FVB mice. The systolic, diastolic and mean blood pressure (BP), heart rate (HR), and ECG of the mice before and after feeding with high fructose (66%) diet and high salt (2%) water were monitored daily for 16 weeks.
Results: A time-dependent hypertension was induced in CFTR+/+ mice after intake of high-fructose + high salt for 16 weeks, as indicated by a significant increase in both diastolic and systolic BP and also mean BP. The development of hypertension increase in systolic, diastolic and mean BP in the CFTR-/- mice was significantly faster (<3 weeks) than that in the CFTR+/+ mice, indicating an important role of CFTR in the development of high-fructose- and high salt-induced hypertension in the mice. The increase in the daytime BP (mean BP112±2.1 vs 121±3.2 mmHg) was significantly higher than that in the night time. CFTR knockout caused an increase in vascular tone and also oxidative stress in the smooth muscle cells, which may be part of the mechanisms for the faster development of hypertension under the stress of high-salt and high-fructose.
Conclusion: Targeted disruption of CFTR gene significantly changed the development of high fructose- and high salt-induced hypertension. The loss of CFTR function may be responsible for the fast development of hypertension in response of the mice to high fructose and high salt diet, implicating a novel and important role of CFTR in the development of hypertension.
- © 2012 by American Heart Association, Inc.