Anti-remodeling efficacy of eprosartan in patients with essential hypertension, and gene polymorphism of angiotensin II type 1 receptors

Aim. To study the effects of long-term eprosartan treatment efficacy on myocardial structure and function in patients with essential arterial hypertension (EAH), and the association of these effects with structural polymorphism of angiotensin II type 1 receptors (AT2RI).
Material and methods. The study included 121 males with Stage II-III EAH (WHO/ISH, 1999), mean age 49.09±8.34 years, with disease duration of 2-15 years. Central hemodynamics parameters and left ventricular myocardial mass (LVMM) were assessed by echocardiography (EchoCG) method. Left ventricular hypertrophy (LVH) was identified, according to the values of LVMM and LVMM index (LVMMI). LVH was diagnosed in LVMMI >134 g/m2. LV diastolic filling was assessed with Doppler EchoCG, by peak rates of early and late filling, and their ratio. Endothelial function was investigated with Doppler ultrasound. Prevalence of alleles and genotypes of polymorphic fragments (A1166C) of angiotensin II type 1 receptor gene was studied. The association of A/C polymorphism with hemodynamic parameters, LVH markers, endothelial function (EF), and eprosartan monotherapy efficacy, was also investigated.
Results. A significant prevalence of A-allele and AA-genotype of AT1RII gene A1166C-polymorphic marker was observed. AC+CC genotypes were associated with more severe LVH, LV diastolic dysfunction, and EF disturbances. With equally high antihypertensive efficacy of 3-month eprosartan therapy, only AA-genotype patients demonstrated substantial LVH regression and complete normalization of vasoregulatory EF.
Conclusion. Eprosartan demonstrated high antihypertensive efficacy in all participants. But only among AA-genotype patients, substantial LVH regression and complete normalization of vasoregulatory EF was observed during 3-month eprosartan therapy.

1. Кобалава Ж.Д., Котовская Ю.В. Артериальная гипертония 2000: ключевые аспекты диагностики и дифференцированной диагностики, профилактики, клиники и лечения. Метод реком. Под ред проф Моисеева В.С. Москва 2001; 208 с: 17-24.

2. Белоусов Ю.Б. Поражение органов-мишеней при артериальной гипертонии. Тер архив 1997; 69: 12-5.

3. Лазебник Л.Б., Милюкова О.М., Комисаренко И.А. Блокаторы рецепторов ангиотензина II. Метод реком. Москва 2001; 56-62.

4. Бражник В.А., Затейщиков Д.А., Сидоренко Б.А. Наследственные факторы и гипертрофия левого желудочка. Кардиология 2000; 3: 68-73.

5. Затейщиков Д.А., Минушкина Л.О., Кудряшова и др. Полиморфизм генов NO–синтетазы и рецептора ангиотензина II 1-го типа и эндотелиальный гемостаз у больных ишемической болезнью сердца. Кардиология 2000; 11: 28-32.

6. Минушкина Л.О., Затейщиков Д.А., Сидоренко Б.Н. и др. Генетические аспекты регуляции эндотелиальной функции при артериальной гипертонии. Кардиология 2000; 3: 68-76.

7. Кобалава Ж.Д., Котовская Ю.В. Чистяков Д.А. и др. Клинико-генетические детерминанты ГЛЖ у больных эссенциальной гипертонией. Кардиология 2001; 7: 39-44.

8. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation 1977; 55: 613-8.

9. Abergel E, Tase M, Bohlader J. Which definition for еchocardiographic left ventricular hypertrophy? Am J Cardiol 1995; 75: 489-503.

10. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-5.

11. Минушкина Л.О., Затейщиков Д.А., Кудряшова О.Ю. и др. Дисфункция эндотелия: связь с полиморфизмом гена рецептора (тип 1) ангиотензина II у больных ишемической болезнью сердца. Кардиология 2000; 1: 20-5.

12. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995-1003.

13. Gemil RM, Drabkin HA. Report of the Second International Work shop on human chromosome 3 mapping. Cytogen Cell Genet 1991; 57: 162-6.

14. Hingorani AD, Brown MJ. A simple molecular assay for the 1166 variant of angiotensin II type 1 receptor gene. Biochem Biophys Res Commun 1995; 231: 725-9.

15. Носиков В.В., Чистяков Д.А., Кобалава Ж.Д. и др. Изучение вклада генов ренин-ангиотензиновой системы в предрасположенность к артериальной гипертонии в московской популяции. Москва 1999; 130-3.

16. Osterop AP, Kofflard MJ, Sandkuiji LA, et al. AT1 receptor gene A/C polymorphism contributes to cardiac hypertrophy in subjects with hypertrophy cardiomiopathy. Hypertension 1998; 32: 825-30.

17. Henrion D, Amant C, Benessiano J, et al. Angiotensin II type 1 receptor gene polymorphism is associated with an increased vascular reactivity in the human mammary artery in vitro. J Vascular Res 1998; 35: 356-62.

18. Escudero X, Lablanche JM, Amouyel P, et al. The angiotensin II type 1 receptor gene polymorphism is associated with coronary artery vasoconstriction. JACC 1997; 129: 486-90.