Faculty Collaboration Database

Fructose stimulates Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. Hypertension 2014 Mar;63(3):e68-73

Date

01/01/2014

Pubmed ID

24379189

DOI

10.1161/HYPERTENSIONAHA.113.02564

Scopus ID

2-s2.0-84894487159 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

The proximal nephron reabsorbs 60% to 70% of the fluid and sodium and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport is implicated in hypertension. Our findings show that a fructose-enriched diet causes salt sensitivity. We hypothesized that fructose stimulates luminal Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. Na/H exchange was measured in rat proximal tubules as the rate of intracellular pH (pHi) recovery in fluorescent units/s. Replacing 5 mmol/L glucose with 5 mmol/L fructose increased the rate of pHi recovery (1.8±0.6 fluorescent units/s; P<0.02; n=8). Staurosporine, a protein kinase C inhibitor, blocked this effect. We studied whether this effect was because of the addition of fructose or removal of glucose. The basal rate of pHi recovery was first tested in the presence of a 0.6-mmol/L glucose and 1, 3, or 5 mmol/L fructose added in a second period. The rate of pHi recovery did not change with 1 mmol/L but it increased with 3 and 5 mmol/L of fructose. Adding 5 mmol/L glucose caused no change. Removal of luminal sodium blocked pHi recovery. With 5.5 mmol/L glucose, angiotensin II (1 pmol/L) did not affect the rate of pHi recovery (change, -1.1±0.5 fluorescent units/s; n=9) but it increased the rate of pHi recovery with 0.6 mmol/L glucose/5 mmol/L fructose (change, 4.0±2.2 fluorescent units/s; P<0.02; n=6). We conclude that fructose stimulates Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. This mechanism is likely dependent on protein kinase C. These results may partially explain the mechanism by which a fructose diet induces hypertension.

Author List

Cabral PD, Hong NJ, Hye Khan MA, Ortiz PA, Beierwaltes WH, Imig JD, Garvin JL

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Biological Transport
Disease Models, Animal
Fructose
Hydrogen-Ion Concentration
Hypertension
Kidney Tubules, Proximal
Rats
Sodium-Hydrogen Exchangers
Sweetening Agents