Original Articles Korean Circulation J 치료받지않은고혈압환자에서혈중단핵구 βark1 의 농도와좌심실질량의비교연구 최봉룡 1 김은지 2 이지은 3 윤지철 1 남중희 1 박성지 1 황진용 1 최동주 1 서

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1 Original Articles Korean Circulation J 치료받지않은고혈압환자에서혈중단핵구 βark1 의 농도와좌심실질량의비교연구 최봉룡 1 김은지 2 이지은 3 윤지철 1 남중희 1 박성지 1 황진용 1 최동주 1 서봉관 1 Association between ARK1 Level of Circulating Mononuclear Leukocytes and Left Ventrcular Mass in Non-treated Hypertensive Patients Bong-Ryong Choi, MD 1, Eun-Ji Kim, BS 2, Ji-Eun Lee, BS 3, Ji-Cheol Yun, MD 1, Jung-Hee Nam, MD 1, Seong-Ji Park, MD 1, Jin-Yong Hwang, MD 1, Dong-Ju Choi, MD 1 and Bong-Gwan Seo, MD 1 1 Department of Interenal Medicine, Cardiovascular Research Center, 2 Pharmacology, 3 Neurobiology, College of Medicine, Gyeongsang National University, Kyungnam, Korea BackgroundBeta-adrenergic receptor Kinase 1 ARK1 is a serine/threonine kinase attached, which inhibits the coupling of -adrenergic receptor with G-protein. Myocardial ARK1 level is usually elevated in heart failure and hypertrophy, but it is not known whether the circulating ARK1 level is related with the degree of cardiac hypertrophy. This study was performed to evaluate the association of the ARK1 level in circulating mononuclear leukocytes MNL in untreated hypertension with left ventricular mass in hypertensive patients. MethodNineteen non-treated hypertensive patients were included for this study. High blood pressure was confirmed when systolic BP is over 150 mmhg or diastolic BP is over 95 mmhg. Echocardiography was performed to evaluate the degree of hypertrophy by measuring the left ventricular mass index LVMI and relative wall thickness RWT, and test the LV function by measuring the ejection fraction EF according to ASE guideline. At the same time, blood was collected from each patient and MNL were isolated by gradient centrifuge with Ficoll-400. Total RNA was purified from MNL and semi-quantitative RT-PCR was performed. After reverse transcription, PCR was done with primers for human ARK1 and GAPDH as external control. ARK1 levels were expressed by ratio to GAPDH level and estimated the relations with clinical and Echocardiographic parameters. ResultWe studied confirmed 19 hypertensive patients 10 men and 9 women, mean age of 50.6 years. Echocardiographically measured indices meansd were as followslvmi g/m 2, PWT and EF %. Ratio of ARK1 levels to GAPDH was from 0.10 to ARK1 levels were correlated with LVMI correlation coefficientr0.502, p0.029 and RWT r0.627, p But Systolic BP r0.009, p0.93, diastolic BP r0.07, p0.85 or EF r0.045, p0.84 were not related to level of ARK1. ConclusionsThe ARK1 level of circulating MNL was correlated well with the degree of the cardiac hypertrophy estimated by LVMI and RWT. This data 1530

2 suggests that activation of sympatho-adrenal system would exert a major role in developing cardiac hypertrophy and we can expect the decreased responsiveness to catecholamine in the heart of hypertensive patients. ARK1 in circulating MNL might be used as a predictor or marker for LV hypertrophy in hypertensive patients. Korean Circulation J 2000;3012: KEY WORDSARK1 beta-adrenergic receptor Kinase 1 Hypertrophy LVMI Left Ventricular Mass Index. 서론 1531

3 대상및방법 대상 1532 방법 Fig. 1. Schematic diagram of M-mode of the left ventricle. The left ventricular interval dimension at enddiastole was measured at on set of the QRS complex and systolic S measurement was done at the maximal excursion of the ventricular septum. Interventricular septum and left ventricular posterior wall thickness were measured at the onset of the QRS complex. AbbreviationsST DVentricular septal thickness at enddiastole. LVD DLeft ventricular internal dimension at end-diastole. LVD SLeft ventricular internal dimension at end-systloe. PWT DLeft ventricular posterobasal free wall thickickness at end-diastole. Korean Circulation J 2000;3012:

4 통계적방법 1533

임상양상 1534 결 Table 1. Clinical characteristics n19 Gender Men 10, Female 9 Age yr 50.4 12.3 Height cm 160.3 10.5 Body weight kg 62.4 14.5 Body surface area m 2 1.66 0.23 SBP mmhg Systolic 168.7 17.

5 임상양상 1534 결 Table 1. Clinical characteristics n19 Gender Men 10, Female 9 Age yr Height cm Body weight kg Body surface area m SBP mmhg Systolic Diastolic Heart rate /min Values are meansd. 과 Table 2. Echocardiographic data n19 LVD S mm LVD D mm ST D mm PWT D mm RWT LVEF % LVM g LVMI g/m Values are meansd. LVD DLeft ventricular internal dimension at enddiastole LVD SLeft ventricular internal dimension at end-systloe ST DVentricular septal thickness at end-diastole PWT DLeft ventricular posterobasal free wall thickickness at end-diastole RWTRelative posterior wall thickickness LVEFLeft ventricular ejection fraction LVMLeft ventricular mass LVMILeft Ventricular mass index 심초음파상의지표 PCR cycle의결정 Fig. 2. Semiquantitative RT-PCR. Semiquantitative reverse transcriptase-polymerase chain reaction RT-PCR was perfomed to determine the adequate cycles for glyceraldehy-de-3-phosphate dehydrogenase GAD- PH and beta-adrenergic receptor kinase 1 ARK1. Fig. 3. Quantitation of PCR product. Proper polymerase chain reaction PCR cycle is determined as glyceraldehyde-3-phosphate dehydrogenase GAD- PH 30 cycle and beta-adrenergic receptor kinase 1 ARK1 33 cycle. Korean Circulation J 2000;3012:

glyceraldehy-de-3-phosphate dehydrogenase GAPDH by SigmaGel with UV exposed photography. Ratio of ARK1 levels to GAPDH was from 0.10 to 0.96 0.

6 ARK1 GAPDH Fig. 4. RT-PCR sample of patients. After completion of PCR, each sample was run on the agarose gel and quantitated relative density of ARK1 compared with glyceraldehy-de-3-phosphate dehydrogenase GAPDH by SigmaGel with UV exposed photography. Ratio of ARK1 levels to GAPDH was from 0.10 to Fig. 5. Correlation between ARK1 and LVMI. ARK1 beta-adrenergic receptor kinase 1. LVMIleft venticular mass index. βark1 발현의반정량분석 Fig. 6. Correlation between ARK1 and RWT. ARK1 beta-adrenergic receptor kinase 1. RWTrelative posterior wall thickensss. 고 찰 1535

7 Fig. 7. Correlation between ARK1 and BP. ARK1 beta-adrenergic receptor kinase 1. SBPsystolic pressure. DBPdiastolic pressure. Fig. 8. Correlation between ARK1 and EF. ARK1 beta-adrenergic receptor kinase 1. EFejection fraction Korean Circulation J 2000;3012:

8 - 요약 연구배경 : 1537

9 대상및방법 : 결과 : 결론 : 1538 중심단어 REFERENCES 1) Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relationof left ventricular and geometry to morbidity and mortality in men and women with essential hypertension. Ann Intern Med ) Levy D, Garrison RJ, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the framingham Heart Study. N Engl J Med ) Casale PN, Deverreux RB, Milner M, Zullo G, Harshfield GA, Pickering TG, et al. Value echocardiographic left ventrucular mass predicting cardiovascular morbid events in hypertensive men. Ann Intern Med ) Kannel WB, Gordon G, Offut D. Left ventricular hypertrophy by electrocardiogrm prevalence, incidence, and mortality in the framingham study. Ann Intern Med ) Krzesinski JM, Rorive G, Van Cauwenberge H. Hypertension and left ventricular hypertrophy. Acta Cardiol ) Devereux RB, Alonso DR, Lamutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assesment of left ventricular hypertrophy Comparison to necropsy finding. Am J Cardiol ) HARVEST Study Group. Structural abnormalities and not diastolic dysfuction are the earliest left ventricular changes in hypertension. Am J Hypertension ) Kim DI, Song JH, Im SW, Park SG, Chung EM, Cha DH, et al. Comparison of left ventricular hypertrophy between hypertensive and chronic renal disease patients. Korean J of Medicine ) Verdechia G, Gatteschi C, Benemio F, Porcellati. Circar-dian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation ) Perloff D, Sokolow M. The prognostic value ambulatory blood pressure. JAMA ) Kupari M, Koskinen P, Virolainen J. Correlates of left ventricular mass in a population sample aged 36 to 37 young focus on life style and salt intake. Circulation ) Verdecchia P, Schillaci G, Borsioni C, Ciucci A, Zampi I, Battistelli M, et al. Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension. J Hypertens 1995 Oct ) de Simone G, Devereux RB, Mureddu GF, Roman MJ, Ganau A, Alderman MH, et al. Influence of obesity on left ventricular midwall mechanics in aterial hypertension. Hypertension 1996 Aug Korean Circulation J 2000;3012:

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012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar