Abstract: SA-PO1110
Influence of Dietary K on Angiotensin II Hypertension in Females
Session Information
- Salt and Hypertension
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Hypertension
- 1104 Hypertension: Clinical and Translational - Salt and Hypertension
Authors
- Veiras, Luciana C., Keck School of Medicine of USC , Los Angeles, California, United States
- Prescott, Jessica E., Keck School of Medicine of USC , Los Angeles, California, United States
- Ralph, Donna, University of Southern California, Los Angeles, California, United States
- McDonough, Alicia A., Keck School of Medicine of USC , Los Angeles, California, United States
Background
Male Sprague Dawley rats (SDR) infused with angiotensin II, “AngII HTN” (400 ng/kg/min, 14 days) exhibit increased Na+ transporter activation by phosphorylation (p) or cleavage (cl) in cortical TAL (NKCC2), DCT (NCC), CNT/CD (ENaC) and increased SPAK kinase. Doubling dietary K+ during AngII HTN prevents NCC, NCCp activation, attributed to ENaC driven K loss.
Female SDR at baseline, compared to males, exhibit lower PT transporter activity, higher volume flow from PT (estimated with lithium clearance, CLi), and more abundant NCC, NCCp and ENaC-cl.
Methods
This study aimed to determine the effect of doubling dietary K (1% to 2%) on female SDR at baseline (1K vs 2K) and during AngII HTN (as above, 1KAngII, 2KAngII), n=6/group.
Results
In 2K vs.1K fed female SDR: plasma [Na] and [K] were unchanged and [aldosterone] doubled; in overnight urine: UV was unchanged, UK doubled, UNa increased 1.5 fold (p=0.02); CLi increased 1.7 fold (p=0.02). 2K vs. 1K diet had no effect on NHE3, NKCC2, NCC, ENaC or SPAK abundance or activation assessed by quantitative immunoblot.
AngII treatment in female SDR raised BP to 193 ± 8 mmHg, not different in 2K vs 1K. UV increased 1.7 (1KAngII) and 1.8 fold (2KAngII) (both p<0.02). UNaV and UKV were not further changed by AngII in either group. CLi increased in 2KAngII vs 2K by 1.7 fold (p=0.04).
In PT paracellular Cldn2 increased 2.2 fold (1KAngII) and 3.8 fold (2KAngII) (p<0.006), AngII increased NHE3 1.4 fold in both 1K and 2 K fed, and increased NHE3p (an inactivation indicator) 1.4 fold in 1KAngII alone.
Cortex (not medulla) NKCC2 and NKCC2p were increased 2.2 and 1.8 fold (p=0.002) in the 1KAngII, and the effect was blunted in 2KAngII (to 1.6 and 1.3 fold, p > 0.1). NCCp was borderline increased in 1KAngII (1.4 fold, p = 0.06) and suppressed 50% in 2KAngII vs 1KAngII (p=0.007). Cortex (not medulla) SPAK, was increased 3 fold in both groups. Alpha ENaC was activated in cortex and medulla (>2 fold, p < 0.01) in both groups. Cldn7 increased 25 (1KAngII) and 50% (2KAng).
Conclusion
The results indicate that in female SDR: 1) doubling K intake reduces apparent PT reabsorption (CLi) independent of abundance of PT transporters or plasma [K] associated with natriuresis and the expected kaliuresis. 2) 2K diet during AngII HTN further increases CLi as well as Cldn2, Cldn7 and blunts the effect of AngII on NKCC, NKCCp and NCCp activation.
Funding
- NIDDK Support