Enhanced responses of blood pressure, renal function, and aldosterone to angiotensin I in the DD genotype are blunted by low sodium intake

FGH Van der Kleij, PE De Jong, RH Henning, D De Zeeuw, G Navis*

*Corresponding author for this work

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Abstract

Angiotensin-converting enzyme (ACE) activity is increased in the DD genotype, but the functional significance for renal function is unknown. Blunted responses of BP and proteinuria to ACE inhibition among DD renal patients during periods of high sodium intake were reported. It was therefore hypothesized that sodium status affects the phenotype in the ACE I/D polymorphism. The effects of angiotensin I (AngI) and AngII among 27 healthy subjects, with both low (50 mmol sodium/d) and liberal (200 mmol sodium/d) sodium intakes, were studied. Baseline mean arterial pressure (MAP) values, renal hemodynamic parameters, and renin-angiotensin system parameters were similar for all genotypes with either sodium intake level. With liberal sodium intake, the increases in MAP, renal vascular resistance, and aldosterone levels during AngI infusion (8 ng/kg per min) were significantly higher for the DD genotype, compared with the ID and H genotypes (all parameters presented as percent changes 95% confidence intervals), with mean MAP increases of 22 +/- 2% (DD genotype), 13 +/- 5% (ID genotype), and 12 +/- 6% (II genotype) (P <0.05), mean increases in renal vascular resistance of 100.1 +/- 19.7% (DD genotype), 73.0 +/- 16.3% (ID genotype), and 63.2 +/- 16.9% (II genotype) (P <0.05), and increases in aldosterone levels of 650 +/- 189% (DD genotype), 343 +/- 71% (ID genotype), and 254 +/- 99% (II genotype) (P <0.05). Also, the decrease in GFR was more pronounced for the DD genotype, with mean decreases of 17.9 +/- 4.7% (DD genotype), 8.8 +/- 3.4% (ID genotype), and 6.4 +/- 5.9% (II genotype) (P <0.05). The effective renal plasma flow, plasma AngII concentration, and plasma renin activity values were similar for the genotypes. In contrast, with low sodium intake, the responses to Angl were similar for all genotypes. The responses to Ang II were also similar for all genotypes, with either sodium intake level. In conclusion, the responses of MAP, renal hemodynamic parameters, and aldosterone concentrations to AngI are enhanced for the DD genotype with liberal but not low sodium intake. These results support the presence of gene-environment interactions between ACE genotypes and dietary sodium intake.

Original languageEnglish
Article numberUNSP 1046-6673/1304-1025
Number of pages9
JournalJournal of the American Society of Nephrology
Volume13
Issue number4
Publication statusPublished - Apr-2002

Keywords

  • CONVERTING-ENZYME GENE
  • DELETION POLYMORPHISM
  • MYOCARDIAL-INFARCTION
  • IGA NEPHROPATHY
  • PROGRESSION
  • RISK
  • ASSOCIATION
  • SYSTEM
  • RENIN
  • RESPONSIVENESS

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