高血圧発症後の持久的運動トレーニングが自然発症:高血圧ラット心臓のニトロ化ストレスに及ぼす影響  [in Japanese] Effect of endurance exercise training on nitrative stress of the heart after the emergence of hypertension in spontaneously hypertensive rats  [in Japanese]

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Author(s)

    • 古川 覚 FURUKAWA SATOSHI
    • 東洋大学ライフデザイン学部健康スポーツ学科 Department of Health Care and Sports, Faculty of Human Life Design, Toyo University
    • 神野 宏司 KOHNO HIROSHI
    • 東洋大学ライフデザイン学部健康スポーツ学科 Department of Health Care and Sports, Faculty of Human Life Design, Toyo University

Abstract

KEIICHI IKEDA目的: 本研究は, 高血圧を発症した自然発症高血圧ラット (SHR) に10週間の持久的運動トレーニングを行わせ, 同週齢のSHRと心臓の3-ニトロチロシン (3-NT) 濃度, スーパーオキシドジスムターゼ (SOD) および一酸化窒素合成酵素 (NOS) の酵素量および活性を比較することにより, SHR心臓のニトロ化ストレスに及ぼす持久的運動トレーニングの効果を検討することを目的とした.対象および方法: 15週齢のオスSHR20匹を, コントロール群 (25wk Cont群) および持久的運動トレーニング群 (25wk Ex群) に10匹ずつ分けた. 25wk Ex群には飼育ケージに取り付けられたカウンター付き回転ホイールにおける自発走トレーニングを10週間行わせた. 持久的運動トレーニング期間終了後, 両群のラットの心臓懸濁液を分画し3-NTの検出, Mn-SODおよびCu, Zn-SODの酵素量および活性の測定, さらに血管内皮型NOS (eNOS) 酵素量の測定を行った. また, 免疫組織染色により心組織の3-NT染色を行った.結果: 持久的運動トレーニングはSHRの安静時収縮期血圧の上昇を抑制しなかった. しかしながら, 持久的運動トレーニングを行った25wk Ex群は25wk Cont群よりもミトコンドリア, 小胞体および原形質膜を含む顆粒画分の3-NT濃度が有意に低く持久的運動トレーニングが心臓のニトロ化を抑制していることを示していた. この変化は心臓の免疫組織染色においても確認することができた. また, 25wk Ex群のMn-SOD量は25wk Cont群よりも増加しており持久的運動トレーニングの効果が観察された.結論: SHRの高血圧発症後の10週間の持久的運動トレーニングは心臓におけるMn-SODを増加させ, 心臓のニトロ化ストレスを軽減することが明らかになった.

Objective: We investigated the effects of exercise training starting after emergence of hypertension (15-week-old) on nitrative stress and protein levels and activities of nitrative stress-related enzymes in the hearts of spontaneously hypertensive rats (SHR).Material and Methods: We examined the hearts of 25-week old (wk) SHR that performed either 10 wk of voluntary exercise training (Ex) or remained intact (Cont). We also analyzed 5 wk and 15 wk SHR in order to determine basal alterations of nitrative stress and enzymes. Starting at 15 weeks old, 25 wk Ex SHR exercised by voluntary running in a wheel-cage for 10 weeks. At the end of the breeding or training period, rats were anesthetized and hearts were collected. We measured the level of nitrotyrosine by the time-resolved fluoroimmunoassay method, the amount of manganese-containing (Mn-) and copper/zinc-containing (Cu, Zn-) superoxide dismutase (SOD), and endothelial nitric oxide synthase (eNOS) in the heart by the western blotting method. Furthermore Mn- and Cu, Zn-SOD and total NOS activity were measured by the spectrometry method.Result: Systolic blood pressure was elevated at 15 wk and remained high until 25 wk Cont SHR. Exercise did not affect the blood pressure. Although there was no significant increase in 3-nitrotyrosine (3-NT) concentration in 100,000g precipitate fractions (P2) of heart homogenate of 15 wk SHR, a significant in crease in 3-NT concentration was observed in that of 25 wk Cont SHR. This increase in 3-NT concentration was significantly attenuated in that of 25 wk Ex SHR. The same alterations of 3-NT levels were observed by immunohistochemical analysis using specific antibody for 3-NT. Protein levels of endothelial nitric oxide synthase (eNOS) in the membrane fractions were reduced in 15 wk and 25 wk Cont SHR compared with those of 5 wk SHR, but not affected by Ex. This evidence was supported by the measurements of total NOS activity in the same fractions. Protein levels of Cu, Zn-SOD were reduced to a greater degree in 25 wk Ex and Cont SHR than in those of 5 wk and 15 wk SHR, but there was no significant effect observed by Ex. The same results were obtained upon measurement of Cu, Zn-SOD activity. However, protein of Mn-SOD increased significantly in 15 wk SHR, compared to that of 5 wk SHR. Although there was no significant difference in Mn-SOD levels between 25 wk Cont SHR and 15 wk SHR, significant increases in Mn-SOD levels and activity were observed in 25 wk Ex SHR, compared with those of 25 wk Cont SHR. This evidence accounts for the significant attenuation of 3-NT formation in the P2 fraction of 25 wk Ex SHR.Conclusion: We conclude that 10 weeks of exercise training after the emergence of hypertension could reduce nitrative stress in the organelle fractions of the heart as a result of the increase in Mn-SOD.

Journal

  • Juntendo Medical Journal

    Juntendo Medical Journal 54(3), 308-317, 2008

    The Juntendo Medical Society

Codes

  • NII Article ID (NAID)
    130004712060
  • Text Lang
    JPN
  • ISSN
    0022-6769
  • Data Source
    J-STAGE 
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