Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats

被引:314
作者
Zalba, G [1 ]
Beaumont, FJ [1 ]
San José, G [1 ]
Fortuño, A [1 ]
Fortuño, MA [1 ]
Etayo, JC [1 ]
Díez, J [1 ]
机构
[1] Univ Navarra, Sch Med, Vasc Pathophysiol Unit, E-31080 Pamplona, Spain
关键词
endothelium; rats; inbred SHR; superoxides; hypertrophy;
D O I
10.1161/01.HYP.35.5.1055
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
This study was designed to test the hypothesis that stimulation of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase is involved in increased vascular superoxide anion (. O-2(-)) production in spontaneously hypertensive rats (SHR). The study was performed in 16-week-old and 30-week-old normotensive Wistar-Kyoto rats (WKY16 and WKY30, respectively) and in 16-week-old and 30-week-old SHR (SHR16 and SHR30, respectively). In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR30-I). Aortic NADH/NADPH oxidase activity was determined by use of chemiluminescence with lucigenin. The expression of p22phox messenger RNA was assessed by competitive reverse transcription-polymerase chain reaction. Vascular responses to acetylcholine were determined by isometric tension studies. Aortic wall structure was studied, determining the media thickness and the cross-sectional area by morphometric analysis. Whereas systolic blood pressure was significantly increased in the 2 groups of hypertensive animals compared with their normotensive controls, no differences were observed in systolic blood pressure between SHR30 and SHR16. No other differences in the parameters measured were found between WKY16 and SHR16. In SHR30 compared with WKY30, we found significantly greater p22phox mRNA level, NADH/NADPH-driven . O-2(-) production, media thickness, and cross-sectional area and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and p22phox expression as the WKY,, group. The vascular functional and morphological parameters were improved in SHR50-I. These findings suggest that an association exists between p22phox gene overexpression and NADH/NADPH overactivity in the aortas of adult SHR. Enhanced NADH/NADPH oxidase-dependent . O-2(-) production may contribute to endothelial dysfunction and vascular hypertrophy in this genetic model of hypertension.
引用
收藏
页码:1055 / 1061
页数:7
相关论文
共 39 条
  • [1] Vasodilator dysfunction in aged spontaneously hypertensive rats:: changes in NO synthase III and soluble guanylyl cyclase expression, and in superoxide anion production
    Bauersachs, J
    Bouloumié, A
    Mülsch, A
    Wiemer, G
    Fleming, I
    Busse, R
    [J]. CARDIOVASCULAR RESEARCH, 1998, 37 (03) : 772 - 779
  • [2] APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE
    BECKMAN, JS
    BECKMAN, TW
    CHEN, J
    MARSHALL, PA
    FREEMAN, BA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) : 1620 - 1624
  • [3] Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production
    Bouloumie, A
    Bauersachs, J
    Linz, W
    Scholkens, BA
    Wiemer, G
    Fleming, I
    Busse, R
    [J]. HYPERTENSION, 1997, 30 (04) : 934 - 941
  • [4] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [5] ENDOTHELIAL DYSFUNCTION AND SUBENDOTHELIAL MONOCYTE MACROPHAGES IN HYPERTENSION - EFFECT OF ANGIOTENSIN CONVERTING ENZYME-INHIBITION
    CLOZEL, M
    KUHN, H
    HEFTI, F
    BAUMGARTNER, HR
    [J]. HYPERTENSION, 1991, 18 (02) : 132 - 141
  • [6] Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats
    Cosentino, F
    Patton, S
    d'Uscio, LV
    Werner, ER
    Werner-Felmayer, G
    Moreau, P
    Malinski, T
    Lüscher, TF
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) : 1530 - 1537
  • [7] DIJKSTRA CD, 1985, IMMUNOLOGY, V54, P589
  • [8] THE GLYCOPROTEIN ENCODED BY THE X-LINKED CHRONIC GRANULOMATOUS-DISEASE LOCUS IS A COMPONENT OF THE NEUTROPHIL CYTOCHROME-B COMPLEX
    DINAUER, MC
    ORKIN, SH
    BROWN, R
    JESAITIS, AJ
    PARKOS, CA
    [J]. NATURE, 1987, 327 (6124) : 717 - 720
  • [9] ACTIVATION OF ENDOTHELIAL L-ARGININE PATHWAY IN RESISTANCE ARTERIES - EFFECT OF AGE AND HYPERTENSION
    DOHI, Y
    THIEL, MA
    BUHLER, FR
    LUSCHER, TF
    [J]. HYPERTENSION, 1990, 16 (02) : 170 - 179
  • [10] Overexpression of Bax protein and enhanced apoptosis in the left ventricle of spontaneously hypertensive rats -: Effects of AT1 blockade with losartan
    Fortuño, MA
    Ravassa, S
    Etayo, JC
    Díez, J
    [J]. HYPERTENSION, 1998, 32 (02) : 280 - 286