Expression of NAD(P)H Oxidase Subunits and Their Contribution to Cardiovascular Damage in Aldosterone/Salt-Induced Hypertensive Rat

被引:23
作者
Park, Young Mee [3 ]
Lim, Bong Hee [3 ]
Touyz, Rhian M. [2 ]
Park, Jeong Bae [1 ]
机构
[1] Kwandong Univ, Coll Med, Cheil Gen Hosp, Dept Med Cardiol, Seoul 100380, South Korea
[2] Univ Ottawa, Samsung Biomed Res Inst, Ottawa, ON, Canada
[3] Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON, Canada
关键词
Aldosterone; Oxidative Stress; NAD(P)H Oxidase; Hypertension;
D O I
10.3346/jkms.2008.23.6.1039
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target-organ damage. Rats were infused with aldosterone (0.75 mu g/hr/day) for 6 weeks and were given 0.9% NaCl +/- Iosartan (30 mg/kg/day), spironolactone (200 mg/kg/day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox), and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.
引用
收藏
页码:1039 / 1045
页数:7
相关论文
共 34 条
[1]  
Barry-Lane PA, 2001, J CLIN INVEST, V108, P1513, DOI 10.1172/JCI200111927
[2]   NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat [J].
Beswick, RA ;
Dorrance, AM ;
Leite, R ;
Webb, RC .
HYPERTENSION, 2001, 38 (05) :1107-1111
[3]   Endothelin-I-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms [J].
Callera, GE ;
Tostes, RC ;
Yogi, A ;
Montezano, ACI ;
Touyz, RM .
CLINICAL SCIENCE, 2006, 110 (02) :243-253
[4]  
Callera GE, 2003, HYPERTENSION, V42, P811, DOI 10.1161/01.HYP.0000088363.65943.6C
[5]   Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22phox in human mononuclear leukocytes [J].
Calò, LA ;
Zaghetto, F ;
Pagnin, E ;
Davis, PA ;
de Mozzi, P ;
Sartorato, P ;
Martire, G ;
Fiore, C ;
Armanini, D .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (04) :1973-1976
[6]   Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR [J].
Chen, X ;
Touyz, RM ;
Park, JB ;
Schiffrin, EL .
HYPERTENSION, 2001, 38 (03) :606-611
[7]   p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats [J].
Fukui, T ;
Ishizaka, N ;
Rajagopalan, S ;
Lauren, JB ;
Capers, Q ;
Taylor, WR ;
Harrison, DG ;
deLeon, H ;
Wilcox, JN ;
Griendling, KK .
CIRCULATION RESEARCH, 1997, 80 (01) :45-51
[8]   Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype [J].
Gerling, IC ;
Sun, Y ;
Ahokas, RA ;
Wodi, LA ;
Bhattacharya, SK ;
Warrington, KJ ;
Postlethwaite, AE ;
Weber, KT .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 285 (02) :H813-H821
[9]   Reactive oxygen species as mediators of angiotensin II signaling [J].
Griendling, KK ;
Ushio-Fukai, M .
REGULATORY PEPTIDES, 2000, 91 (1-3) :21-27
[10]   Functional association of NOX1 with P22PHOX in vascular smooth muscle cells [J].
Hanna, IR ;
Hilenski, LL ;
Dikalova, A ;
Taniyama, Y ;
Dikalov, S ;
Lyle, A ;
Qum, MT ;
Lassègue, B ;
Griendling, KK .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (10) :1542-1549