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(Hypertension. 2000;36:411.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Sensitivity Is Associated With the Angiotensin II Type 1 Receptor A¹¹⁶⁶C Polymorphism in Essential Hypertensives on a High Sodium Diet

Wilko Spiering; Abraham A. Kroon; Monique M. J. J. Fuss-Lejeune; Mat J. A. P. Daemen; Peter W. de Leeuw

From the Departments of Internal Medicine (W.S., A.A.K., M.M.J.J.F-L., P.W. de L.) and Pathology (M.J.A.P.D.), Cardiovascular Research Institute Maastricht, Maastricht University and University Hospital Maastricht, Netherlands.

Correspondence to Peter W. de Leeuw, University Hospital Maastricht, Department of Internal Medicine, PO Box 5800, 6202 AZ Maastricht, Netherlands. E-mail P.deleeuw{at}intmed.unimaas.nl

Abstract—Several investigations have shown heterogeneity in the functional responses to angiotensin II (Ang II) in patients with essential hypertension. The present study was initiated to evaluate whether the A¹¹⁶⁶C polymorphism of the Ang II type 1 receptor (AT₁R) gene contributes to this variability in Ang II responses. After 7 days of a high-sodium diet (220 mmol Na⁺ per day), we measured in 42 essential hypertensive patients blood pressure, heart rate, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), active plasma renin concentration, aldosterone, and atrial natriuretic peptide (ANP) before and during Ang II infusion (increasing doses of 0.3, 1.0, and 3.0 ng/kg per minute). Calculated variables were filtration fraction and renal vascular resistance (RVR). Patients in the 3 genotype groups (AA: n=14; AC: n=17; CC: n=11) were matched for gender, age, and body mass index. At baseline, CC patients had decreased GFR (P=0.06) and aldosterone (P<0.05) and increased ANP (P<0.05) compared with AA patients. Moreover, responses of ERPF, GFR, and RVR to the lowest concentration of Ang II (0.3 ng/kg per minute) were more pronounced in CC patients than in AA patients (ERPF/GFR: P<0.05; RVR: P=0.07), whereas maximal responses were all comparable between the groups. Heart rate was decreased at all levels of Ang II infusion in CC patients, while it did not change in AA or AC patients. There were no differences in responses of active plasma renin concentration, aldosterone, and ANP to Ang II between the 3 groups. From these data, we conclude that the C allele of the AT₁R A¹¹⁶⁶C polymorphism is associated with increased sensitivity but not reactivity to Ang II. An augmented response to Ang II may well be responsible for the increased incidence of cardiovascular abnormalities found in patients with 1 or 2 C alleles.

Key Words: angiotensin II • receptors, angiotensin II • polymorphism

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