Developing approaches to treating arterial hypertension in regard to possible pathways of angiotensin II synthesis

Aim. To study antihypertensive effects of AT1-receptor blocker eprosartan and ACE inhibitor enalapril, in regard to leading pathway of angiotensin II (AT II) synthesis among arterial hypertension (AH) patients with various functional status of renin-angiotensin-aldosterone system (RAAS). Material and methods. In total, 54 AH patients were examined. RAAS parameters and chymase activity were measured at rest and after orthostatic and captopril tests. Thirty-eight out of 54 patients were included into an open comparative cross-over two-group study, being administered eprosartan or enalapril. Antihypertensive effect was assessed after 8 weeks of treatment, by office blood pressure (BP) levels and 24-hour BP monitoring (BMP) results. Results. Basic criteria for identifying leading AT II synthesis pathway were proposed: antihypertensive reaction type in captopril test and baseline level of plasma chymase activity. Assessing eprosartan and enalapril treatment efficacy, it turned out that both agents had significant, similar antihypertensive effects, with eprosartan’s dominating influence on pulse BP. Eprosartan therapy was more effective in low-renin AH patients. Enalapril was less effective than eprosartan in patients with alternative, chymase-dependent pathway of AT II synthesis. Conclusion. Leading pathways of AT II synthesis in AH patients might be BP reduction in captopril test and baseline level of plasma chymase activity. Eprosartan therapy was more effective in low-renin and severe AH, that might be linked to its effects on alternative pathway of AT II synthesis.

1. Hollenberg NK. Imрlications of species difference for clinical investigation: studies on the R-A-S.Hypertension 2000; 35: 150-4.

2. Рекомендации по профилактике, диагностике и лечению артериальной гипертензии. Российские рекомендации (второй пересмотр). Комитет экспертов Всероссийского научного общества кардиологов. Секция артериальной гипертонии ВНОК. Москва 2004.

3. Арабидзе Г.Г., Белова Л.А., Чихладзе Н.М. и др. Активность химотрипсиноподобных протеиназ у больных ишемической болезнью сердца, артериальной гипертонией, неспецифическим аорто-артериитом. Тер архив 2000; 11: 39-43.

4. Danilov S, Savoie F, Lenoir B , et al. Development of enzymelinked immunoassays for human angiotensin I converting enzyme suitable for large-scale studies. J Hypertens 1996; 14(6): 19-29.

5. Kang SH, Fuchs MS. An improvement in the Hummel chymotrypsin assay. Anal. Biochem 1973; 54(1): 262-5.

6. Roks A, Buikema H, Donckier J, et al. The renin-angiotensin system and vascular function. The role of AII, ACE and alternative conversion of AI. Heart Vessel 1997; 12: 119-24.

7. Weir MR, Dzau VJ. The RAAS: a specific target for hypertension managment. Am J Hypertens 1999; 12: 205-13.

8. Arakawa K, Ogihara T, Limura O, et al. Evaluation of clinical usefulness of TCV-116 (Candesartan Cilexitil) in patients with essential hypertension, double blind, parallel group-comparison study using enalapril maleat as control drug (in Japanese). Rinsho Iyaku 1996; 12: 2613-61.

9. Gavras I, Gavras H. Effects of eprosartan versus enalapril in hypertensive patients on the renin-angiotensin-aldosteron system and parameters: results from a 26-week, double-blind, multicentre study. Curr Med Res Opin 1999; 15(1): 15-24.

10. Sega R. Efficacy and safety of eprosartan in sever hypertension. Blood Press 1999; 8: 114-21.

11. Laragh JH. When is it useful to inhibit the RAS to treating. J Cadiovasc Pharmacol 1985; 7(4): 86-91.

12. Jamerson KA. Rationale for angiotensin II receptor blockers in patients with low-renin hypertension.Am J Kid Dis 2000; 36(1): 24-30.

13. Levine B. Effects of eprosartan and enalaprilin in the treatment of black hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Curr Med Res Opin 1999; 15(1): 25-32.

14. Ohlstein EH, Brooks DP, Feuerstein GZ, et al. Inhibition of sympathetic outflow by the angiotensin II receptor antagonist, eprosartan, but not by losartan, valsartan or irbesartan: relationship to differences in prejunctional angiotensin II receptor blockade. Pharmacology 1997; 55: 244-51.