Republican Specialized Center of Cardiology, Tashkent, Uzbekistan.
*Corresponding author: Gulnoz A. Khamidullaeva, Ph, Arterial Hypertension Department, Republican Specialized Center of Cardiology, 4, Osiyo str., 100052 Tashkent, Uzbekistan. Tel: 998-93-5769955; 998-71-2670295
Background: to study of antihypertensive and vasoprotective efficacy of nebivolol according with arterial hypertension candidate genes carriage in Uzbek hypertensive patients.
Material and methods: The study included 52 Uzbek men with Stage I-II of arterial hypertension. Flow mediated dilation (FMD) of the brachial artery and intimae-media thickness (IMT) of common carotid artery were measured by ultrasonographic method. Genomic DNA extracted from peripheral blood. PCR, PCR-restriction and visualization of were performed. Nebivolol prescribed as monotherapy for 12 weeks.
Results: Therapy with nebivolol in a daily average doze 4.6±2.39 mg demonstrated antihypertensive efficacy independently of studied genetic polymorphism carriage. The association of vasoprotective efficacy of nebivolol along with complete normalization of FMD and reliable reduction of the IMT was revealed in carriers of 4b/4b genotype of eNOS, -9/-9 genotype of B2BKR, MM and МТ genotypes of AGT and of Gln/Gln genotype of β2-AR. For achievement of equal antihypertensive efficacy in the carriers of Glu-allele of β2-AR gene in comparison with the carriers of Gln-allele nebivolol was used in a daily doze 6.81±5.19 mg vs. 4.76±2.46 mg (р=0.013). The FMD normalization was marked only in the carriers of Gln-allelle.
Conclusions: The results of the study have shown the high antihypertensive efficacy and reliable vasoprotection of nebivolol monotherapy in Uzbek hypertensive patients – carriers of 4b/4b genotype of eNOS, -9/-9 genotype of B2BKR, MM and МТ genotypes of AGT and of Gln27Gln genotype of β2-AR.
1. Castellano M, Muiesan ML, Rizzoni D, et al. Angiotensin-converting enzyme gene I/D polymorphism and arterial wall thickness in a general population. Circulation 1995; 91:2721-4.
2. Hixson JE, Powers PK. Detection and characterization of new mutations in the human angiotensinogen gene (AGT). Hum Genet 1995; 96(1):110-2.
3. Britten MB, Schachinger V, Dimmeler Sб et al. eNOS polymorphism is associated with coronary endothelial dysfunction. Eur Heart J 1999; 20: Abstract 907: Suppl. P.144.
4. Gainer JV, Brown NJ, Bachvarova M. Altered frequency of a promoter of the kinin B2receptor gene in hypertensive African-Americans. Am J Hyprtens 2000; 13:1268-1273.
5. Bengtsson K, Orho-Melander M, Elander OM, et al. β2-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes. Hypertension 2001; 37:1303- 1308.
6. Benjafield AV, Jeyasingam CL, Nyholt DR, et al. G-protein β3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension 1998; 32:1094-1097.
7. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340:1111-5.
8. Eliseyeva MR, Khamidullaeva GA, Srojidinova NZ, Abdullaeva GJ, et al. Molecular- genetic aspects of Essential Hypertension. Tashkent: SHARK, 2009.
9. Belousov UB, Leonova MV. Clinical efficacy of new beta-blocker nebivolol in patients with arterial hypertension (Results of multicentre study). Kardiologiia 2000; 9:27-32
10. Heltser BI, Kotelnikov VN, Savchenko SV. Functional biochemical characteristics of Nebivolol vessel dilatation efficacy in patients with arterial hypertension. Therapeutic Archive 2002; 12:34-37.
11. Eliseyeva MR, Azimova NN, Abdullaeva IN. Influence of longtime therapy with Nebilet on myocardium remodeling processes and endothelial dysfunction in patients with essential hypertension. Tashkent: Information letter # 0007, 2002.
12. Khamidullaeva GA, Karimova IA, Eliseyeva MR, Muhamedov RS. Clinical and organ protective efficacy of nebivolol in patients with essential hypertension depending 4a/4b polymorphism of eNOS gene. J Theoretical and Clinical Medicine 2004; 3:47-50.
13. Broeders AW, Doevedans PA, Bekkers BC, et al. Nebivolol: a third generation β-blocker that augments vascular nitric oxide release. Circulation 2000; V.102:677- 683.
14. Gao Y, Nagao T, Bond R, et al. Nebivolol induces endothelium – depended relaxation of conine coronary arteries. J Card Pharmacology 1991; 7:964-969.
15. Dzau VJ. Tissue renin-angiotensin system: physiologic and pharmacologic implications. Circulation. 1988; 77(suppl I):I1-I13.
16. Berk ВС, Alexander RW. Biology of the vascular wall in hypertension. In: Renner RM, Ed. The Kidney. Philadelphia: W.B. Saunders, 1996; 2049-2070.
Int J Biomed. 2010;1(1):9-13.© 2010 International Medical Research and Development Corporation. All rights reserved.
