title: Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients.
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.
authors.affiliation: Chair of Nephrology and Postgraduate School of Nephrology, University of Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Manunta
authors.forename: D
authors.initials: D
authors.lastname: Cusi
authors.forename: C
authors.initials: C
authors.lastname: Barlassina
authors.forename: M
authors.initials: M
authors.lastname: Righetti
authors.forename: C
authors.initials: C
authors.lastname: Lanzani
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.forename: L
authors.initials: L
authors.lastname: Buzzi
authors.forename: L
authors.initials: L
authors.lastname: Citterio
authors.forename: P
authors.initials: P
authors.lastname: Stella
authors.forename: R
authors.initials: R
authors.lastname: Rivera
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D004232:Diuretics; D005665:Furosemide; D011188:Potassium; D012964:Sodium; D012965:Sodium Chloride; D000099291:Adducins