P. Manunta et al., ALPHA-ADDUCIN POLYMORPHISMS AND RENAL SODIUM HANDLING IN ESSENTIAL HYPERTENSIVE PATIENTS, Kidney international, 53(6), 1998, pp. 1471-1478
The relationship between blood pressure and sodium (Na) excretion is l
ess steep in hypertension caused by increased renal tubular reabsorpti
on. We recently demonstrated that one mutation in rat alpha-adducin ge
ne: (I) is responsible for approximately 50% of the hypertension of MH
S rats, and (2) stimulates tubular Na-K pump activity when transfected
in renal epithelial cell, suggesting that its pressor effect may occu
r because an increased tubular reabsorption. Linkage and association s
tudies demonstrated that the alpha-adducin locus is relevant for human
hypertension. A point mutation (G460W) was found in human alpha-adduc
in gene, the 460W variant (G/W) is more frequent in hypertensives than
in normotensives. The aim of this study was to test whether acute cha
nges in body Na may differently affect blood pressure in humans as a f
unction of alpha-adducin genotype. The pressure-natriuresis relationsh
ip was analyzed in 108 hypertensives using two different acute maneuve
rs: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (3
10 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homo
zygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with
similar blood pressure, age, body mass index, Sender, plasma and urin
ary sodium and potassium. In basal condition G/W-W/W patients showed a
lower plasma renin activity and fractional excretion of Na. In either
case the pressure-natriuresis relationship was less steep in G/W-W/W
than in G/G patients, obviously negative for Na depletion with furosem
ide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mu mol/min, P < 0.03)
, and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/m
u mol/min, P < 0.001). The finding of reduced slope after Na depletion
or Na load supports the hypothesis that, as MHS rats, humans bearing
one W alpha-adducin variant display an increased of renal tubular sodi
um reabsorption.