American Journal of Life Sciences

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Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients

Received: 23 October 2014    Accepted: 25 October 2014    Published: 24 November 2014
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Abstract

Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.

DOI 10.11648/j.ajls.s.2015030104.11
Published in American Journal of Life Sciences (Volume 3, Issue 1-4, January 2015)

This article belongs to the Special Issue Pharmacogenomics & Personalized Medicine

Page(s) 1-6
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Hypertension, Calciumchannel Blockers, Zelnidipine, Nitrendipine, eNOS, Polymorphism

References
[1] Chobanian A V, Bakris G L, Black H R, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report[J]. JAMA. 2003, 289(19): 2560-2572.
[2] Xu B, Xu Z, Xu X, et al. Prevalence, awareness, treatment, and control of hypertension among residents in Guangdong Province, China, 2004 to 2007[J]. Circ Cardiovasc Qual Outcomes. 2013, 6(2): 217-222.
[3] Sica D A. Pharmacotherapy review: calcium channel blockers[J]. J Clin Hypertens (Greenwich). 2006, 8(1): 53-56.
[4] Lederballe P O. Calcium blockade in arterial hypertension. Review[J]. Hypertension. 1983, 5(4 Pt 2): I74-I79.
[5] Tikhonov D B, Zhorov B S. Structural model for dihydropyridine binding to L-type calcium channels[J]. J Biol Chem. 2009, 284(28): 19006-19017.
[6] Zhao Y, Zhai D, He H, et al. Effects of CYP3A5, MDR1 and CACNA1C polymorphisms on the oral disposition and response of nimodipine in a Chinese cohort[J]. Eur J Clin Pharmacol. 2009, 65(6): 579-584.
[7] Beitelshees A L, Navare H, Wang D, et al. CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response[J]. Circ Cardiovasc Genet. 2009, 2(4): 362-370.
[8] Kamide K, Yang J, Matayoshi T, et al. Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers[J]. Circ J. 2009, 73(4): 732-740.
[9] Sugimoto K, Katsuya T, Kamide K, et al. Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study[J]. Int J Hypertens. 2010, 2010: 196307.
[10] Beitelshees A L, Navare H, Wang D, et al. CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response[J]. Circ Cardiovasc Genet. 2009, 2(4): 362-370.
[11] Bremer T, Man A, Kask K, et al. CACNA1C polymorphisms are associated with the efficacy of calcium channel blockers in the treatment of hypertension[J]. Pharmacogenomics. 2006, 7(3): 271-279.
[12] Kamide K, Yang J, Matayoshi T, et al. Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers[J]. Circ J. 2009, 73(4): 732-740.
[13] Liao P, Yu D, Lu S, et al. Smooth muscle-selective alternatively spliced exon generates functional variation in Cav1.2 calcium channels[J]. J Biol Chem. 2004, 279(48): 50329-50335.
[14] Johnson A D, Newton-Cheh C, Chasman D I, et al. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals[J]. Hypertension. 2011, 57(5): 903-910.
[15] Huang P L, Huang Z, Mashimo H, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase[J]. Nature. 1995, 377(6546): 239-242.
[16] Hyndman M E, Parsons H G, Verma S, et al. The T-786-->C mutation in endothelial nitric oxide synthase is associated with hypertension[J]. Hypertension. 2002, 39(4): 919-922.
[17] Kimura Y, Hirooka Y, Sagara Y, et al. Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity[J]. Clin Exp Hypertens. 2007, 29(1): 13-21.
[18] Wang C J, Zhao J B, Xu J L, et al. [Meta-analysis on the association of G894T polymorphism in endothelial nitric oxide synthase gene and essential hypertension in Chinese population][J]. Zhonghua Liu Xing Bing Xue Za Zhi. 2009, 30(8): 845-849.
[19] Li Y Y. Endothelial nitric oxide synthase G894T gene polymorphism and essential hypertension in the Chinese population: a meta-analysis involving 11,248 subjects[J]. Intern Med. 2011, 50(19): 2099-2106.
[20] Zintzaras E, Kitsios G, Stefanidis I. Endothelial NO synthase gene polymorphisms and hypertension: a meta-analysis[J]. Hypertension. 2006, 48(4): 700-710.
[21] Jachymova M, Horky K, Bultas J, et al. Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy[J]. Biochem Biophys Res Commun. 2001, 284(2): 426-430.
[22] Kehrl J H, Sinnarajah S. RGS2: a multifunctional regulator of G-protein signaling[J]. Int J Biochem Cell Biol. 2002, 34(5): 432-438.
[23] Semplicini A, Strapazzon G, Papparella I, et al. RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients[J]. J Hypertens. 2010, 28(5): 1104-1108.
[24] Sugimoto K, Katsuya T, Kamide K, et al. Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study[J]. Int J Hypertens. 2010, 2010: 196307.
[25] Semplicini A, Lenzini L, Sartori M, et al. Reduced expression of regulator of G-protein signaling 2 (RGS2) in hypertensive patients increases calcium mobilization and ERK1/2 phosphorylation induced by angiotensin II[J]. J Hypertens. 2006, 24(6): 1115-1124.
[26] Wellington K, Scott L J. Azelnidipine[J]. Drugs. 2003, 63(23): 2613-2621, 2623-2624.
[27] Furukawa T, Nukada T, Namiki Y, et al. Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes[J]. Eur J Pharmacol. 2009, 613(1-3): 100-107.
[28] Noda K, Hosoya M, Nakajima S, et al. Anti-atherogenic effects of the combination therapy with olmesartan and azelnidipine in diabetic apolipoprotein E-deficient mice[J]. Tohoku J Exp Med. 2012, 228(4): 305-315.
[29] Nakano K, Egashira K, Ohtani K, et al. Azelnidipine has anti-atherosclerotic effects independent of its blood pressure-lowering actions in monkeys and mice[J]. Atherosclerosis. 2008, 196(1): 172-179.
[30] Miyazaki S, Hamada T, Hirata S, et al. Effects of azelnidipine on uric acid metabolism in patients with essential hypertension[J]. Clin Exp Hypertens. 2014.
[31] Kopf D, Schmitz H, Beyer J, et al. A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy[J]. Diabetes Nutr Metab. 2001, 14(5): 245-252.
[32] Rump L C, Oberhauser V, Schwertfeger E, et al. Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients[J]. J Hypertens. 2000, 18(8): 1115-1119.
[33] Rahn K H, Barenbrock M, Fritschka E, et al. Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial[J]. Lancet. 1999, 354(9188): 1415-1420.
[34] Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace[J]. Circulation. 2006, 113(13): 1708-1714.
[35] Ortiz P A, Garvin J L. Trafficking and activation of eNOS in epithelial cells[J]. Acta Physiol Scand. 2003, 179(2): 107-114.
[36] Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace[J]. Circulation. 2006, 113(13): 1708-1714.
[37] Huang P L, Huang Z, Mashimo H, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase[J]. Nature. 1995, 377(6546): 239-242.
[38] Hyndman M E, Parsons H G, Verma S, et al. The T-786-->C mutation in endothelial nitric oxide synthase is associated with hypertension[J]. Hypertension. 2002, 39(4): 919-922.
[39] Veldman B A, Spiering W, Doevendans P A, et al. The Glu298Asp polymorphism of the NOS 3 gene as a determinant of the baseline production of nitric oxide[J]. J Hypertens. 2002, 20(10): 2023-2027.
[40] Huang B S, Leenen F H. Sympathoinhibitory and depressor effects of amlodipine in spontaneously hypertensive rats[J]. J Cardiovasc Pharmacol. 2003, 42(2): 153-160.
[41] Kimura Y, Hirooka Y, Sagara Y, et al. Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric oxide synthase in the brain and inhibits sympathetic nerve activity[J]. Clin Exp Hypertens. 2007, 29(1): 13-21.
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    Zhiying Luo, Fazhong He, Jianquan Luo, Wei Zhang. (2014). Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients. American Journal of Life Sciences, 3(1-4), 1-6. https://doi.org/10.11648/j.ajls.s.2015030104.11

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    Zhiying Luo; Fazhong He; Jianquan Luo; Wei Zhang. Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients. Am. J. Life Sci. 2014, 3(1-4), 1-6. doi: 10.11648/j.ajls.s.2015030104.11

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    AMA Style

    Zhiying Luo, Fazhong He, Jianquan Luo, Wei Zhang. Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients. Am J Life Sci. 2014;3(1-4):1-6. doi: 10.11648/j.ajls.s.2015030104.11

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  • @article{10.11648/j.ajls.s.2015030104.11,
      author = {Zhiying Luo and Fazhong He and Jianquan Luo and Wei Zhang},
      title = {Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients},
      journal = {American Journal of Life Sciences},
      volume = {3},
      number = {1-4},
      pages = {1-6},
      doi = {10.11648/j.ajls.s.2015030104.11},
      url = {https://doi.org/10.11648/j.ajls.s.2015030104.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030104.11},
      abstract = {Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.},
     year = {2014}
    }
    

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  • TY  - JOUR
    T1  - Relationship between eNOS 894G>T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients
    AU  - Zhiying Luo
    AU  - Fazhong He
    AU  - Jianquan Luo
    AU  - Wei Zhang
    Y1  - 2014/11/24
    PY  - 2014
    N1  - https://doi.org/10.11648/j.ajls.s.2015030104.11
    DO  - 10.11648/j.ajls.s.2015030104.11
    T2  - American Journal of Life Sciences
    JF  - American Journal of Life Sciences
    JO  - American Journal of Life Sciences
    SP  - 1
    EP  - 6
    PB  - Science Publishing Group
    SN  - 2328-5737
    UR  - https://doi.org/10.11648/j.ajls.s.2015030104.11
    AB  - Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.
    VL  - 3
    IS  - 1-4
    ER  - 

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Author Information
  • Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

  • Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

  • Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

  • Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

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