Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Effect of Oryeongsan on Spontaneously Hypertensive Rat decrease of Blood Pressure and Vasodilatory

오령산(五苓散)의 본태성 고혈압 동물모델에서 혈압강하 및 혈관 이완 효과

  • Jang, Youn Jae (Department of Phygiology, College of Korean Medicine, Wonkwnag University) ;
  • Kim, Hye Yoom (Department of Phygiology, College of Korean Medicine, Wonkwnag University) ;
  • Hong, Mi Hyeon (Department of Phygiology, College of Korean Medicine, Wonkwnag University) ;
  • Yoon, Jung Joo (Department of Phygiology, College of Korean Medicine, Wonkwnag University) ;
  • Lee, Ho Sub (Department of Phygiology, College of Korean Medicine, Wonkwnag University) ;
  • Kang, Dae Gill (Department of Phygiology, College of Korean Medicine, Wonkwnag University)
  • 장윤재 (원광대학교 한의과대학 생리학교실) ;
  • 김혜윰 (원광대학교 한의과대학 생리학교실) ;
  • 홍미현 (원광대학교 한의과대학 생리학교실) ;
  • 윤정주 (원광대학교 한의과대학 생리학교실) ;
  • 이호섭 (원광대학교 한의과대학 생리학교실) ;
  • 강대길 (원광대학교 한의과대학 생리학교실)
  • Received : 2022.07.22
  • Accepted : 2022.08.25
  • Published : 2022.08.31
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Abstract

Oryeongsan (ORS), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP). Then, 1 mL/kg of vehicle (distilled water) or 1.5, 3 g/kg of ORS extract were administered orally once a day for 4 weeks. SBP and diastolic blood pressure (DBP) were measured at weeks 1, 2, 3 and 4. At the end of the experiment, blood was collected, and heart were removed for histology. By the 2 weeks after initiation of treatment, the ORS treated group had significantly lower SBP than SHR rats. The ORS treatment significantly improved blood pressure and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in ORS treated group hypertensive rats. Furthermore, an increase in fibrotic area has been observed in SHR rats compared with Wistar-Kyoto rats (WKY). Furthermore, administration of ORS significantly attenuated cardiac fibrosis in hypertensive rats. Therefore, these findings suggest that ORS has a protective effect on heart failure by alleviating hypertensive heart disease and cardiovascular dysfunction in SHR.

Keywords

Acknowledgement

본 논문의 연구는 원광대학교 (2021)의 지원을 받아 수행되었으며 이에 감사드립니다.

References

  1. Katholi RE, Couri DM. Left ventricular hypertrophy: Major risk factor in patients with hypertension: Update and practical clinical applications. Int. J. Hypertens. 2011;495349.
  2. Mancia G, Omboni S, Parati G. The importance of blood pressure variability in hypertension. Blood Press Monit. 2000;5:S9-S15. https://doi.org/10.1097/00126097-200005001-00003
  3. Creemers EE. Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. Cardiovasc. Res. 2011;89:265-272. https://doi.org/10.1093/cvr/cvq308
  4. Eriguchi M. Tsuruya K, Haruyama N, Yamada S, Tanaka S, Suehiro T, Noguchi, H, Masutani K, Torisu K, Kitazono T. Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease. Kidney Int. 2014;87:16-127.
  5. Cho E, Kim M, Ko YS, Lee HY, Song M, Kim HK, Cho WY, Jo SK. Role of inflammation in the pathogenesis of cardiorenal syndrome in a rat myocardial infarction model. Nephrol. Dial. Transplant. 2013;28:2766-2778. https://doi.org/10.1093/ndt/gft376
  6. Cardinale JP, Sriramula S, Pariaut R, Guggilam A, Mariappan N, Elks C, Francis J. HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. Hypertension 2010;56:437-444. https://doi.org/10.1161/HYPERTENSIONAHA.110.154567
  7. Elks CM, Mariappan N, Haque M, Guggilam A, Majid DS, Francis J. Chronic NF-{kappa}B blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR. Am. J. Physiol. Renal Physiol. 2009;296:F298-F305. https://doi.org/10.1152/ajprenal.90628.2008
  8. Moubarak M, Jabbour H, Smayra V, Chouery E, Saliba Y, Jebara V, Fares N. Cardiorenal syndrome in hypertensive rats: Microalbuminuria, inflammation and ventricular hypertrophy. Physiol. Res. 2012;61:13-24.
  9. Liu Y, Zhang R, Qu H, Wu J, Li L, Tang Y. Endothelial microparticles activate endothelial cells to facilitate the inflammatory response. Mol. Med. Rep. 2017;15:1291-1296. https://doi.org/10.3892/mmr.2017.6113
  10. Hsueh WA, Quinones MA. Creager MJ, Endothelium in insulin resistance and diabetes. Diabetes Rev. 1997;5:343-52.
  11. S Godo, H Shimokawa. Endothelial Functions. Arterioscler Thromb Vasc Biol. 2017;Sep;37(9):e108-e114.
  12. Busse R, Fleming I. The endothelial organ. Curr Op Cardiol. 1993;8:719-27. https://doi.org/10.1097/00001573-199309000-00002
  13. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323:27-36. https://doi.org/10.1056/NEJM199007053230106
  14. Gibbons GH, Dzau VJ. Molecular therapy for vascular diseases. Science. 1996;272:689-93. https://doi.org/10.1126/science.272.5262.689
  15. Reiling N, Kroncke R, Ulmer AJ. Nitric oxide of synthase:expression the endothelial, Ca2+/calmodulin-dependent isoform in human B and T lymphocytes. Eur J Immunol. 1996;26:511-6. https://doi.org/10.1002/eji.1830260302
  16. Shaul PW, North AJ, Wu LC. Endothelial nitric oxide synthase is expressed in cultured human bronchiolar epithelium. J Clin Invest. 1994;94:2231-6. https://doi.org/10.1172/JCI117585
  17. Chou TC, Yen MH, Li CY, Ding YA. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension. 1998;31:643-8. https://doi.org/10.1161/01.HYP.31.2.643
  18. Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, PL Li, Ritter JK. Role of Nitric Oxide in the Cardiovascular and Renal Systems. Int J Mol Sci. 2018 Sep 3;19(9):2605. https://doi.org/10.3390/ijms19092605
  19. Waghe P, Sarath TS, Gupta P, Kandasamy K, Choudhury S, Kutty HS, Mishra SK, Sarkar SN. Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling. Chem. Biol. Interact. 2015;237:104-114. https://doi.org/10.1016/j.cbi.2015.06.014
  20. Ichiki T, Usui, M, Kato M, Funakoshi Y, Ito K, Egashira K, Takeshita A. Downregulation of angiotensin II type 1 receptor gene transcription by nitric oxide. Hypertension 1998;31:342-348. https://doi.org/10.1161/01.HYP.31.1.342
  21. Flanagan ET, Buckley MM, Aherne CM, Lainis F, Sattar M, Johns EJ. Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats. Exp. Physiol. 2008;93:1058-1064. https://doi.org/10.1113/expphysiol.2008.043216
  22. Grossi L. Hydrogen sulfide induces nitric oxide release from nitrite. Bioorg. Med. Chem. Lett. 2009;19:6092-6094. https://doi.org/10.1016/j.bmcl.2009.09.030
  23. JY Kang, KW Kang, MJ Jeong, HJ Kim, IS Jang, A Survey of Hypertension Treatment in Korean Medicine. The Journal of Internal Korean Medicine. 2016;37(6):1022-1029. https://doi.org/10.22246/jikm.2016.37.6.1022
  24. Brouwers S, Sudano I, Kokubo Y, Sulaica EM. Arterial hypertension. Lancet. 2021; Jul 17;398(10296): 249-261. https://doi.org/10.1016/S0140-6736(21)00221-X
  25. Liu W, Tang F, Deng Y, Li X, Lan T, Zhang X. Berberine reduces fibronectin and collagen accumulation in rat glomerular mesangial cells cultured under high glucose condition. Mol Cell Biochem. 2009;325:99. https://doi.org/10.1007/s11010-008-0024-y
  26. He L, Rong X, Jiang J, M Liu, P Q, Li L. Amelioration of anti-cancer agent adriamycin-induced nephritic syndrome in rats by Wulingsan (Gorei-San), a blended traditional Chinese herbal medicine. Food Chem Toxicol. 2008;46:1452. https://doi.org/10.1016/j.fct.2007.12.005
  27. Katholi RE, Couri DM. Left ventricular hypertrophy: major risk factor in patients with hypertension: update and practical clinical applications. Int J Hypertens. 2011;495349.
  28. Messerli FH, Rimoldi SF, Bangalore S. The transition from hypertension to heart failure: contemporary update. JACC Heart Fail. 2017;5: 543-551. https://doi.org/10.1016/j.jchf.2017.04.012
  29. Pravenec M, Kren V, Landa V, Mlejnek P, Musilova A, Silhavy J, Simakova M, Zidek V. Recent progress in the genetics of spontaneously hypertensive rats. Physiol Res. 2014;63(Suppl 1):S1-8.
  30. Hultstrom M. Development of structural kidney damage in spontaneously hypertensive rats. J Hypertens. 2012;Jun:30(6):1087-91. https://doi.org/10.1097/HJH.0b013e328352b89a
  31. Pinto YM, Paul M, Ganten D. Lessons from rat models of hypertension:From Goldblatt to genetic engineering. Cardiovasc. Res. 1998;39:77-88. https://doi.org/10.1016/S0008-6363(98)00077-7
  32. Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J. 1963;27:282-293. https://doi.org/10.1253/jcj.27.282
  33. Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation 2003;108:560-565. https://doi.org/10.1161/01.CIR.0000081775.72651.B6
  34. Conrad CH, Brooks WW, Hayes JA, Sen S, Robinson KG, Bing OH. Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat. Circulation 1995;91: 161-170. https://doi.org/10.1161/01.CIR.91.1.161
  35. Bing OH, Brooks WW, Robinson KG, Slawsky MT, Hayes JA, Litwin SE, Sen S, Conrad CH. The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure. J. Mol. Cell. Cardiol. 1995;27:383-396. https://doi.org/10.1016/S0022-2828(08)80035-1
  36. Friberg P, Sundelin B, Bohman SO, Bobik A, Nilsson H, Wickman A, Gustafsson H, Petersen J, Adams MA. Renin-angiotensin system in neonatal rats: Induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism. Kidney Int. 1994;45:485-492. https://doi.org/10.1038/ki.1994.63
  37. Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA. Angiotensin II regulates nephrogenesis and renal vascular development. Am. J. Physiol. 1995;269:F110-F115.
  38. Shibasaki Y, Masaki H, Nishiue T, Nishikawa M, Matsubara H, Iwasaka T. Angiotensin II type 1 receptor antagonist, losartan, causes regression of left ventricular hypertrophy in end-stage renal disease. Nephron. 2002;90(3):256-61. https://doi.org/10.1159/000049060
  39. Kim HY, Ahn YM, Na SW, Jang YJ, Kang DG, Lee HS, Cho KW. Oryeongsan (Wulingsan) ameliorates impaired ANP secretion of atria from spontaneously hypertensive rats. Biomed Pharmacother. 2022;146:112433. https://doi.org/10.1016/j.biopha.2021.112433
  40. Lerman LO, Kurtz TW, Touyz RM, Ellison DH, Chade AR, Crowley SD, Mattson DL, Mullins JJ, Osborn J, Eirin A, Reckelhoff JF, Iadecola C, Coffman TM. Animal Models of Hypertension: A Scientific Statement From the American Heart Association. Hypertension. 2019;73(6):e87-e120
  41. Escudero EM, Hurtado de MCC, Perez NG, Tufare AL. Echocardiographic assessment of left ventricular midwall mechanics in spontaneously hypertensive rats. Eur J Echocardiogr, 2004;5(3);169-175, https://doi.org/10.1016/j.euje.2003.11.004
  42. Frohlich ED. An updated concept of left ventricular hypertrophy risk in hypertension. Ochsner J. 2009;9:181-190.
  43. Raman SV. The hypertensive heart. J. Am. Coll. Cardiol. 2010;55:91-96. https://doi.org/10.1016/j.jacc.2009.07.059
  44. Devereux RB, Pickering TG, Alderman MH, Chien S, Borer JS. Laragh JH. Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables. Hypertension 1987;9: 53-60.
  45. Zanchetti A. Cardiac hypertrophy as a target of antihypertensive therapy. Nat Rev Cardiol. 2010;7:66-67. https://doi.org/10.1038/nrcardio.2009.229
  46. Heagerty AM, Aalkjaer C, Bund SJ, Korsgaard N, Mulvany MJ. Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension, 1993;21:391-397. https://doi.org/10.1161/01.HYP.21.4.391
  47. Mitchell CJ, Churchward-Venne TA, West DW, Burd NA, Breen L, Baker SK, Phillips SM. Resistance exercise load does not determine training-mediated hypertrophic gains in young men. J Appl Physiol, 2012;113:71-77. https://doi.org/10.1152/japplphysiol.00307.2012
  48. Intengan HD, Schiffrin EL. Vascular remodeling in hypertension:Roles of apoptosis, inflammation, and fibrosis. Hypertension 2001;38: 581-587. https://doi.org/10.1161/hy09t1.096249
  49. Mitchell CJ, Churchward-Venne TA, Parise G, Bellamy L, Baker SK, Smith K, Atherton PJ, Phillips SM. Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men. PLoS ONE, 2014;9:e89431. https://doi.org/10.1371/journal.pone.0089431
  50. Chou TC, Yen MH, Li CY, Ding YA. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension 1998;31:643-648. https://doi.org/10.1161/01.HYP.31.2.643