Abstract: FR-PO320
Exogenous Mineralocorticoid Administration and Acute Salt Loading Effects on NCC Expression and Activity in Hypertensives with Raised Aldosterone/Renin Ratio (ARR)
Session Information
- Hypertension and CVD: Mechanisms - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Wu, Aihua, The University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia
- Wolley, Martin, The University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia
- Cowley, Diane, The University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia
- Gordon, Richard, The University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia
- Fenton, Robert, Aarhus University, Aarhus, Denmark
- Stowasser, Michael, The University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia
Background
Primary aldosteronism (PA) is a common form of hypertension (HTN) caused by autonomous aldosterone (Aldo) production. Aldo is the major endogenous mineralocorticoid regulating sodium (Na) reabsorption by stimulating the Na-Cl cotransporter (NCC) and the epithelial Na channel (ENaC) in the renal distal tubule. Potassium (K) may also regulate NCC. Exogenous mineralocorticoid and salt loading suppress plasma Aldo, and affect differently NCC and ENaC in human and murine studies.
Methods
Urine samples were collected before and after fludrocortisone suppression testing (FST; fludrocortisone administration and orally salt loading for 4 days) from 13 subjects (10 with HTN and raised ARR and 3 cured of PA by unilateral adrenalectomy); and saline suppression testing (SST; 2L saline infusion over 4h) from 9 subjects (5 with HTN and raised ARR and 4 cured of PA). Urinary exosomes were analysed by immunoblotting.
Results
Significant increases in abundances of NCC (mean 2.97 fold, p=0.04) and pNCC (mean 2.06 fold, p=0.03) by day 4 of FST were observed in 10 with HTN and raised ARR, yet no clear trends of NCC and pNCC were observed in the 3 cured of PA . There were no significant changes in abundance of prostasin, cleaved γ-ENaC and NKCC2 post FST in all 13 subjects, but cleaved γ-ENaC rose post FST (mean 1.17 fold, p=0.05) among the 10 with HTN and raised ARR. There were trends observed towards decreases in abundance of NCC (p=0.09) and pNCC (p=0.07) in 5 with HTN and raised ARR undergoing SST, but not in 4 cure of PA where NCC and pNCC were already low at baseline. The abundances of cleaved γ-ENaC and NKCC2 were unchanged. Plasma Aldo droped in both subjects with HTN and raised ARR (from 328.6 to 180.8 pM, p=0.07) and subjects cured of PA (from 153.75 to 57.25 pM, p=0.05) after SST, but plasma K was unchanged.
Conclusion
Variation of NCC abundance and phosphorylation during FST and SST is detectable in human urinary exosomes. Exogenous mineralocorticoid administration is associated with increases in exosomal NCC and pNCC. The decreases in NCC and pNCC abundance during SST in HTN with raised ARR suggest acute salt loading may induce salt excretion by reducing NCC expression and activity, which may relate to a reduction in plasma Aldo but is independent of plasma K.
Funding
- Private Foundation Support