Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients

Kidney Int. 1998 Jun;53(6):1471-8. doi: 10.1046/j.1523-1755.1998.00931.x.

Abstract

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary 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 sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/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 sodium reabsorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Calmodulin-Binding Proteins / genetics*
  • Diuretics / pharmacology
  • Female
  • Furosemide / pharmacology
  • Humans
  • Hypertension / genetics*
  • Hypertension / metabolism*
  • Kidney / metabolism*
  • Male
  • Middle Aged
  • Natriuresis / drug effects
  • Natriuresis / physiology
  • Polymorphism, Genetic / genetics*
  • Potassium / urine
  • Sodium / metabolism*
  • Sodium Chloride / pharmacology

Substances

  • Calmodulin-Binding Proteins
  • Diuretics
  • adducin
  • Sodium Chloride
  • Furosemide
  • Sodium
  • Potassium