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(Hypertension. 2001;38:1278.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Type 2 Receptors and Cardiac Hypertrophy in Women With Hypertrophic Cardiomyopathy

Jaap Deinum; Jeanette M.G. van Gool; Marcel J.M. Kofflard; Folkert J. ten Cate; A.H. Jan Danser

From the Cardiovascular Research Institute of the Erasmus University Rotterdam (COEUR), Departments of Internal Medicine (J.D. J.M.G.v.G.), Cardiology (M.J.M.K. F.J.t.C.), and Pharmacology (A.H.J.D.), Erasmus University Rotterdam, Rotterdam, The Netherlands.

Correspondence to Dr A.H.J. Danser, PhD, Department of Pharmacology, Room EE1418b, Erasmus University Rotterdam, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail danser{at}farma.fgg.eur.nl

The development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1 (AT₁-R) and angiotensin II type 2 (AT₂-R) receptors, respectively. Here we investigated the effect of the AT₂-R gene A/C³¹²³ polymorphism, located in the 3' untranslated region of exon 3, on left ventricular mass index (LVMI) in 103 genetically independent subjects with HCM (age, 12 to 81 years). LVMI and interventricular septum thickness were determined by 2D echocardiography. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were determined by immunoradiometric or fluorometric assays, and genotyping was performed by polymerase chain reaction. In men, no associations between AT₂-R genotype and any of the measured parameters were observed, whereas in women, LVMI decreased with the number of C alleles (211±19, 201±18, and 152±10 g/m² in women with the AA, AC, and CC genotype, respectively; P=0.015). Similar C allele–related decreases in women were observed for interventricular septum thickness (P=0.13), Wigle score (P=0.05), plasma renin (P=0.03), and plasma prorenin (P=0.26). Multiple regression analysis revealed that the AT₂-R C allele–related effect on LVMI (ß=-30.7±11.1, P=0.010) occurred independently of plasma renin, the AT₁-R gene A/C¹¹⁶⁶ polymorphism, or the ACE gene I/D polymorphism. In conclusion, AT₂-Rs modulate cardiac hypertrophy in women with HCM, independently of the circulating renin-angiotensin system. These data support the contention that AT₂-Rs mediate antitrophic effects in humans.

Key Words: cardiomyopathy • hypertrophy • receptors, angiotensin II • renin

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