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Enhanced Responses of Blood Pressure, Renal Function, and Aldosterone to Angiotensin I in the DD Genotype Are Blunted by Low Sodium Intake

Frank G. H. van der Kleij^*, Paul E. de Jong^*, Rob H. Henning^*, Dick de Zeeuw^* and Gerjan Navis^*

*Groningen University Institute for Drug Exploration, Department of Internal Medicine, Division of Nephrology, and Department of Clinical Pharmacology, University Hospital Groningen and State University Groningen, Groningen, The Netherlands.

Correspondence to Dr. Gerjan Navis, Department of Internal Medicine, Division of Nephrology, University Hospital Groningen, Hanzeplein 1 P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Phone: +31-50-3612621; Fax: +31-50-3619310; E-mail: g.j.navis@ int.azg.nl

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 II 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 AngI were similar for all genotypes. The responses to AngII 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.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673