Japanese
TitleアンジオテンシンII受容体遮断薬およびCa拮抗薬の慢性経口投与は, 高血圧ラットの循環調節の高い線形性を低下させ, 低い非線形性を亢進させる
Subtitle原著
Authors大波敏子*, 熊谷裕生*, 佐方克史*, 大坂元久**, 滝本千恵*, 飯ヶ谷嘉門*, 猿田享男*
Authors(kana)
Organization*慶應義塾大学医学部内科学, **日本医科大学老人病研究所
Journal循環制御
Volume25
Number2
Page158-168
Year/Month2004/
Article原著
Publisher日本循環制御医学会
Abstract「要旨」これまで私どもは高血圧自然発症ラット(SHR)では, 正常血圧ラット(WKY)に比べて神経性循環調節の線形性が高く, 非線形性が低いことを報告してきた. そこで, 本研究ではカンデサルタンとアムロジピンの14日間の経口投与により, SHRの腎交感神経活動(RSNA)と血圧(BP)およびRSNAと腎血流量(RBF)の相関の線形性および非線形性がどのように変化するかを検討した. カンデサルタン, アムロジピン両群で有意な血圧低下および腎血流量の増加を認めた. 一方, 腎交感神経活動はカンデサルタン群で有意に抑制されたが, アムロジピン群では有意には抑制されなかった. RSNAからBPおよびRSNAからRBFへの伝達関数のコヒーレンスは, カンデサルタン群, アムロジピン群でvehicle群と比較して有意に低下し, 相互情報量(線形性と非線形性)は有意に増加した. このことより, SHRの高い線形性が低下し, 低い非線形性が増加したことが示された. これらの結果からカンデサルタン, アムロジピンは高血圧患者の不良な予後を改善することが期待される.
Practice基礎医学・関連科学
KeywordsHypertension, Sympathetic nerve activity, angiotensin II recepter blocker, Ca channel blocker, nonlinearity, coherence
English
TitleCandesartan or Amlodipine Reduced the Linear and Increased the Nonlinear Correlation of Sympathetic Nerve Activity with Blood Pressure in Conscious Hypertensive Rats
Subtitle
AuthorsToshiko Onami*, Hiroo Kumagai*, Katsufumi Sakata*, Motohisa Osaka**, Chie Takimoto*, Kamon Iigaya*, Takao Saruta*
Authors(kana)
Organization*Department of Internal Medicine, Keio University School of Medicine, **Institute of Gerontology, Nippon Medical School
JournalCirculation Control
Volume25
Number2
Page158-168
Year/Month2004/
ArticleReport
PublisherJapan Society of Circulation Control
AbstractObjective：Patients with reduced nonlinear component of heart rate regulation show a poor prognosis. We previously reported that the linear correlation between renal sympathetic nerve activity(RSNA)and blood pressure(BP)or RSNA and renal blood flow(RBF)was significantly higher and the nonlinear correlation was lower in spontaneously hypertensive rats(SHR)than in Wistar-Kyoto rats. In the present study, we examined whether the linear and nonlinear correlation between RSNA and BP or RBF would change in SHR orally treated with angiotensin II receptor blocker(candesartan)or calcium channel blocker(amlodipine)for 2 weeks. Also, to elucidate mechanisms underlying the reduced linearity by amlodipine, we examined whether the linear and nonlinear correlation between RSNA and BP or RBF would change in SHR treated with amlodipine and L-NAME orally for 2 weeks. Methods：By recording BP, RSNA, heart rate, and ipsilateral RBF simultaneously in conscious state, we compared the linear(coherence of transfer function)and nonlinear(mutual information method)correlations among RSNA, BP and RBF in SHR treated with drugs. <Protocol 1>Candesartan(1mg/kg/day, n=13), amlodipine(5mg/kg/day, n=7)or vehicle(n=7)was given orally for 2 weeks to SHRs. <Protocol 2>Combination of amlodipine(5mg/kg/day)and L-NAME(1.5mg!kg/day, n=9), amlodipine(5mg/kg/day, n=7), or vehicle was given orally for 2 weeks to SHRs. Results：<Protocol 1>Mean RSNA was significantly decreased in the candesartan group despite lower BP and larger RBE whereas RSNA did not decrease in the amlodipine group. The coherence between RSNA and BP or between RSNA and RBF at 0-1.0 Hz was significantly reduced in both candesartan and amlodipine groups compared with vehicle group. In contrast, mutual information of the correlation between RSNA and BP or RSNA and RBF increased in both candesaratan and amlodipine groups. <Protocol 2>The coherence between RSNA and BP or RBF was significantly higher and mutual information was lower in SHR treated with amlodipine plus L-NAME compared with SHR treated with only amlodipine. Conclusions：The data regarding candesartan suggest that blockade of the renin-angiotensin system and sympathetic nervous system contributes to the reduced linearity and increased nonlinearity. However, since this is not the case with amlodipine, increased nitric oxide contributed to the improved neural regulation by the calcium channel blocker. Since potentiated sympathetic nerve activity and high linearity/low nonlinearity are risk factors for cardiovascular events, drugs that reduce sympathetic nerve activity and normalize the neural regulation are beneficial to prevent cardiovascular events in hypertenslve patlents.
PracticeBasic medicine
KeywordsHypertension, Sympathetic nerve activity, angiotensin II recepter blocker, Ca channel blocker, nonlinearity, coherence

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