본태성고혈압흰쥐의 신장에서 지구성 운동에 의한 Cytochrome P-450 isoforms mRNA 발현변화
Changes of Cytochrome P-450 Isoforms mRNA Expression by Treadmill Exercise in the kidney of Spontaneously Hypertensive Rat
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고혈압은 신장손상과 관련되어 있다. 이에 이 연구는 본태성 고혈압 쥐의 신장 내 cytochrome P450 (CYP)4A1, 4A2, 4A3 mRNA의 발현, 심박수, 혈압(수축기, 이완기)의 변화를 조사하고 12주간의 지구성 운동수행을 하여 그 차이에 따른 효과를 규명하는데 목적을 두고 조사하였다. 연구대상은 6주령된 수컷 본태성 고혈압 쥐(spontaneously hypertensive rat; SHR, n=14)와 비교집단인 Wistar Kyoto 쥐(WKY, n=14)를 대상으로 WKY 비교집단(WKY, n=7)과 WKY 운동집단(WKY-EX, n=7), SHR 비교집단(SHR,n=7)과 SHR 운동집단(SHR-EX, n=7)으로 구분하였다. 지구성운동은 rodent 트레드밀 운동을 하였으며, 방법은 주 5회, 1일 1시간씩 0% 경사도에서 12주 동안 2주 간격으로 트레드밀 속도를 증가시켜 훈련시켰다. 심박수와 혈압의 변화는 SHR 비교집단이 다른 집단에 비해 유의하게 높게(p<.05) 나타났지만, SHR의운동집단에서는 SHR 비교집단에 비해 유의하게 감소(p<.05)되었다. CYP 4A1, 2, 3의 mRNA는 SHR 비교집단이 다른 집단에 비해 유의하게 높게(p<.05) 나타났지만, SHR의 운동집단에서는 SHR 비교집단에 비해 유의하게 감소(p<.05)되었다. 이상의 결과를 종합하면 12주간의 지구성운동은 본태성고혈압의 신장 내 CYP 4A1, 2, 3의 mRNA 발현의 억제와 항고혈압효과를 볼 수 있었다. 따라서 지구성운동은 고혈압으로 인한 신장의 기능을 개선시켜 신장을 보호할 수 있을 것으로 생각된다
Abstract
Hypertension is associated with renal injury. The present study was designed to examine the changes of kidney by cytochrome P 450 (CYP) 4A1, 4A2, 4A3 mRNA in kidney, heart rate (HR), and blood pressure (BP) (systolic, diastolic) on tail cuff and investigated the effect of endurance exercise for 12 weeks on spontaneously hypertension rats (SHR). Total 28 animals (14 SHR; 14 WKY) were used and divided in WKY control group (WKY, n=7), WKY exercise group (WKY-EX, n=7), SHR control group (SHR, n=7) and SHR exercise group (SHR-EX, n=7). Exercise was performed in rodent treadmill for 5days/wks, 1 hour/day, 12weeks gradually (1∼2week: 1.6m/min, 3∼4week: 1.7m/min, 5∼6week:1.8m/min, 7week: 1.9m/min, 8∼12week: 2.0m/min). Results showed that the HR and BP in SHR were higher than other groups, interestingly, HR and BP in SHR-EX was significantly decreased compared to SHR groups. The CYP 4A1, 4A2, 4A3 mRNA expression in kidney of SHR were higher than other groups, whereas, SHR-EX showed markedly inhibited of CYP 4A1, 4A2, 4A3 mRNA expression than SHR groups. These results suggest that endurance prolonged exercise for 12 week in SHR might be prevented or inhibited to exert positive antihypertensive effects by decreasing CYP 4A1, 4A2, 4A3 mRNA expression in kidney of SHR. Thus, endurance exercise training may be helpful to improvement of renal function in kidney of SHR.
참고문헌 (41)
- 이진, "8주간 유산소운동이 고혈압 흰쥐 신장에서 Angiotensin II 발현과 Apoptosis에 미치는 영향", 한국체육학회지, 46(1), pp.681~690 (2007), 한국체육학회
- Arakawa,K, "Antihypertensive mechanism of exercise", J Hypertens, 11, pp.223~229 (1993)
- Baylis,C, "Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage", J Clin Invest, 90, pp.278~281 (1992)
- Brenner,B.M, "Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury", Am J Kidney Dis, 23, pp.171~175 (1994)
- Capdevila,J, "The oxidative metabolism of ara chidonic acid by purified P-450", Biochem Biophys Res Commun, 101, pp.1357~1363 (1981)
- Cederholm,J, "The relationship of blood pressure to blood glucose and leisure time activity", Acta Med Scan, 219, pp.37~46 (1986)
- Finkelstein,M, "Inborn error of steroid biosynthesis", Physiol Rev, 59, pp.353~406 (1979)
- Frohlich, E. D, "The heart in hypertension", N Engl J Med, 327, pp.998~1008 (1992)
- Fujihara,C.K, "Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition", Am Physiol, 266(5), pp.697~705 (1994)
- Gebremedhin,D, "Role of cytochrome p-45 in elevating renal vas cular tone in spontaneously hypertensive rats", J Vasc Res, 30, pp.53~60 (1993)
- Gibson,G.G, "Comparative aspects of the mammalian cytochrome P-450 IV gene family", Xenobiotica, 19, pp.1123~1148 (1989)
- Gobѐ,G.C, "Cellualr events in experimental unilateral ischemic renal atrophy and in regeneration after contralateral nephrectomy", Lab Invest, 63, pp.770~779 (1990)
- Hardwick,J.P, "Isolation,comple men tary DNA sequence,and regulation of rat hepatic lauric acid ω-hydroxylase", J Bilo Chem, 262, pp.801~810 (1987)
- Hercule,H.C, "Contribution of cytochrome p450 4A isoforms to renal functional response to inhibition of nitric oxide production in the rat", J Physiol, 551, pp.971~979 (2003)
- Husain,K, "Oxidative injury due to chronic oxide syntheses inhibition in rat:effect of regular exercise on the heart", Biochem Biophys Acta, 1587, pp.75~82 (2002)
- Husain,K, "Interaction of exercise training and chronic NOS inhibition on blood pressure,heart rate,NO and antioxidants in plasma of rats", Pathophysiology, 10, pp.47~56 (2003)
- Ikeda,T, "Effects of swim training on blood pressure,catecholamine and prostaglandin in spontaneously hypertensive rats", JPN Heart J, 35 (1994)
- Imig, J. D, "Affere nt arteriolar responses to ANG Ⅱ involve activation of PLA2 and modulation by lipoxygenase and p-45 pathways", Am J Physiol Renal Physiol, 273, pp.F274~282 (1997)
- Imig,J.D, "Elevated renovascular tone in young sponta neously hypertensive rats; role of cytoch rome p-450", Hypertension, 22, pp.357~364 (1993)
- Iwai,N, "Isolation of preferentially expressed genes in the kidneys of hypertensive rats", Hypertension, 17, pp.161~169 (1991)
- Kelly,G, "Antihypertensive effects of aerobic exercise.A brief mec a-analytic review of randomized controled trials", Am J Hypertens, 7, pp.115~119 (1994)
- Kingwell,B.A, "Four weeks of cycle training increase basal production of nitric oxide frome the forearm", Am J Physiol, 22, pp.H1070~1077 (1997)
- Kimura,S, "The rat clofibrate-inducible CYP4A subfamily Ⅱ.cDNA seq uence of IVA3,mapping of the CYP4A locus to mouse chromosome 4,and coordinate and tissue-specific regulation of the CYP4A genes", DNA, 8, pp.517~525 (1989)
- Kohzuki,M, "Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure", J Hypertens, 19, pp.1877~1882 (2001)
- Linda,S.R, "Exercise and Hypertension", Med Sci Sports Exerc, 3603, pp.533~553 (2004)
- Meredith,I.T, "Exercise training lowers resting renal but not cardiac sympathetic activity in humans", Hypertension, 18, pp.575~582 (1991)
- Messerli,F.H, "Left ventricular hypertrophy:an independent risk factor", J Cardiovasc Pharmacol, 17, pp.S59~67 (1991)
- Nakanishi,K, "Role of renal medullary flow in development of L-NAME hypertension in rats", Am J Physiol, 268, pp.317~323 (1995)
- Nelson,D.R, "P-450 superfamily:update on new sequences.gene mapping.accession numbers and nomenclature", Pharmacogenetics, 6, pp.1~42 (1996)
- Omata,K, "Age-related changes in renal cytochrome P-450 ara chidonicacid metabolism in spontaneously hypertensive rats", Am J Physiol, 262, pp.F8~F16 (1992)
- Powell,P.K, "Metabolism of ara chidonic acid to 20-hydroxy-5,8,11,14-eicosatetraenoic acid by P-450 enzymes in human liver:involvement of CYP 4F2 and CYP4A11", J Pharmacol Exp Ther, 285, pp.1327~1336 (1998)
- Rice,T, "Commingling and Segregation Analysis of Blood Pressure in a French-Canadian Population", Am J Hum Genet, 46, pp.37~44 (1990)
- Sacerdoti,D, "Renal cytochrome P-450-dependent metabolism of arachid onic acid in cirrhotic rats", J Hepatol, 12, pp.230~235 (1991)
- Scarborough,P.E, "P-450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues", Drug Metab Rev, 31, pp.205~234 (1999)
- Simpson,A.E, "The cytochrome P-450 4(CYP4)family", Gen Pharmacol, 28, pp.351~359 (1997)
- Stec,D.E, "Renal cytochrome P-450A activity and salt-sensitivity in spontaneously hyperte nsive rats", Hypertension, 27, pp.1329~1336 (1996)
- Stec,D.E, "Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats", Hypertension, 29, pp.315~319 (1997)
- Su,P, "Inhibition of renal arachidonic acid omega-hydroxylase activity with ABT re duces blood pressure in the SHR", Am J Physiol, 275, pp.R426~438 (1998)
- Wang,M.H, "Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys", Am J Physiol, 276, pp.F246~253 (1999)
- Wright,JT Jr, "African american study of kidney disease and hypertension study group:Effect of blood pressure lowering and anti-hypertensive drug class on progression of hypertensive kidney disease:results from the AASK trial", JAMA, 288, pp.2421~2431 (2002)
- Wu,R.Z, "Clinical study on conducting physical exercise in lowering blood pressure of hypertensive patients and influencing their endocrine hormones", Zhongguo Zhong Xi Jie He Zhi, 21(12), pp.897~899 (2001)