Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension

Objective The basolateral Na pump drives renotubular
reabsorption. In cultured renal cells, mutant adducins, as
well as sub-nanomolar ouabain concentrations, stimulate
the Na–K pump.
Methods To determine whether these factors interact and
affect Na handling and blood pressure (BP) in vivo, we
studied 155 untreated hypertensive patients subdivided on
the basis of their plasma endogenous ouabain or a-adducin
genotype (ADD1 Gly460Trp-rs4961).
Results Under basal conditions, proximal tubular
reabsorption and plasma Na were higher in patients with
mutated Trp ADD1 or increased endogenous ouabain
(PU0.002 and 0.05, respectively). BPs were higher in the
high plasma endogenous ouabain group (PU0.001).
Following volume loading, the increment in BP (7.73 vs.
4.81mmHg) and the slopes of the relationship between BP
and Na excretion were greater [0.017W0.002 vs.
0.009W0.003mmHg/(mEq min)] in ADD1 Trp vs. ADD1 Gly
carriers (P<0.05). BP changes were similar, whereas the
slopes of the relationship between BP and Na excretion
were lower [0.016W0.003 vs. 0.008W0.002mmHg/
(mEq min)] in patients with low vs. high endogenous
ouabain (P<0.05). In patients with high endogenous
ouabain, volume loading increased the BP in the ADD1 Trp
group but not in the Gly group (P<0.05). Thus, patients with
ADD1 Trp alleles are sensitive to salt and tubular Na
reabsorption remains elevated after volume expansion.
Conclusion With saline loading, BP changes are similar
in high and low endogenous ouabain patients, whereas
tubular Na reabsorption increases in the high endogenous
ouabain group. Saline loading unmasks differences in renal
Na handling in patients with mutant adducin or high
endogenous ouabain and exposes an interaction of
endogenous ouabain and Trp alleles on BP.