Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension

被引:147
作者
Vaziri, ND [1 ]
Oveisi, F [1 ]
Ding, YX [1 ]
机构
[1] Univ Calif Irvine, Dept Med, Div Nephrol & Hypertens, Irvine, CA 92717 USA
关键词
chronic renal failure; hypertension; oxygen free radicals; antioxidants; nitric oxide; lazaroid; arteriosclerosis;
D O I
10.1046/j.1523-1755.1998.00947.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Earlier studies have demonstrated increased oxygen free radical (OFR) activity, diminished antioxidant capacity and reduced OFR-inactivating enzymes in chronic renal failure (CRF). Via inactivation of nitric oxide (NO), oxidation of arachidonic acid and a direct vasoconstrictive action. OFR can potentially raise blood pressure (BP). This study was designed to test the hypothesis that increased OFR activity may contribute to CRF hypertension. Four weeks after 5/6 nephrectomy rats were treated for two weeks with either lazaroid, a potent antioxidant and lipid peroxidation inhibitor (CRF-LZ group), or vehicle alone (CRF group) by daily gastric gavage. The control group was sham operated and placebo treated. The CRF group exhibited significant increases in BP and plasma lipid peroxidation product, malondialdehyde (MDA), indicating enhanced OFR activity. This was accompanied by decreased urinary nitrate/nitrite (NOx) excretion suggesting depressed NO production. LZ therapy normalized plasma MDA and significantly ameliorated CRF-induced hypertension Both MDA and blood pressure (BP) rose to values seen in the untreated CRF group within two weeks after termination of LZ therapy. Intravenous administration of the hydroxyl radical scavenger, dimethylthiourea (DMTU), significantly lowered BP and raised urinary NOx excretion. However, no discernible effects were found with either superoxide dismutase or catalase (superoxide and H2O2 quenchers). The results suggest that increased OFR activity is, in part, responsible for CRF-associated HTN. The study further points to hydroxyl radicals as the major source of OFR in CRF animals. If substantiated in humans, antioxidant therapy becomes a logical adjunct in the management of CRF.
引用
收藏
页码:1748 / 1754
页数:7
相关论文
共 38 条
  • [1] THIOL MODIFICATION IN H2O2-INDUCED AND THROMBOXANE-INDUCED VASOCONSTRICTION AND BRONCHOCONSTRICTION IN RAT PERFUSED LUNG
    ATZORI, L
    OLAFSDOTTIR, K
    CORRIGA, AM
    BANNENBERG, G
    RYRFELDT, A
    MOLDEUS, P
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1991, 71 (04) : 1309 - 1314
  • [2] NANOGRAM NITRITE AND NITRATE DETERMINATION IN ENVIRONMENTAL AND BIOLOGICAL-MATERIALS BY VANADIUM(III) REDUCTION WITH CHEMI-LUMINESCENCE DETECTION
    BRAMAN, RS
    HENDRIX, SA
    [J]. ANALYTICAL CHEMISTRY, 1989, 61 (24) : 2715 - 2718
  • [3] SYMPATHETIC OVERACTIVITY IN PATIENTS WITH CHRONIC-RENAL-FAILURE
    CONVERSE, RL
    JACOBSEN, TN
    TOTO, RD
    JOST, CMT
    COSENTINO, F
    FOUADTARAZI, F
    VICTOR, RG
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (27) : 1912 - 1918
  • [4] REDUCED ERYTHROCYTE DEFENSE-MECHANISMS AGAINST FREE-RADICAL TOXICITY IN PATIENTS WITH CHRONIC-RENAL-FAILURE
    DURAK, I
    AKYOL, O
    BASESME, E
    CANBOLAT, O
    KAVUTCU, M
    [J]. NEPHRON, 1994, 66 (01): : 76 - 80
  • [5] SIGNIFICANCE OF THE VASCULAR RENIN-ANGIOTENSIN PATHWAY
    DZAU, VJ
    [J]. HYPERTENSION, 1986, 8 (07) : 553 - 559
  • [6] ESCBACH JW, 1985, KIDNEY INT, V28, P1
  • [7] SUPEROXIDE ANION IS INVOLVED IN THE BREAKDOWN OF ENDOTHELIUM-DERIVED VASCULAR RELAXING FACTOR
    GRYGLEWSKI, RJ
    PALMER, RMJ
    MONCADA, S
    [J]. NATURE, 1986, 320 (6061) : 454 - 456
  • [8] Kaupke C J, 1993, ASAIO J, V39, pM614
  • [9] KAUPKE CJ, 1994, J AM SOC NEPHROL, V4, P1874
  • [10] KESTENBAUM RS, 1990, NEPHRON, V55, P251