Japanese
Titlenoradrenalineの昇圧反応はcaptoprilで抑制される ―bradykinin B2受容体を介するnitric oxide産生増加の関与―
Subtitle原著
Authors湊口信也*, 伊藤裕康**, 横山仁美*, 越路正敏*, 宇野嘉弘*, 藤原久義*
Authors(kana)
Organization*岐阜大学医学部第2内科, **澤田病院
Journal循環制御
Volume18
Number1
Page45-50
Year/Month1997/
Article原著
Publisher日本循環制御医学会
Abstract「要旨」［目的］captoprilはnoradrenaline(NA)による昇圧反応を抑制する. この抑制効果のメカニズムを検討することにある. ［対象と方法］Sprague-Dawley ratを用い, ペントバルビタール麻酔, 人工呼吸下に, 右眼より脊椎管にpithing rodを挿入し, pithed ratを作製した. 下記の薬剤投与前後にて, NA(0.1, 0.2, 0.5, 1, 2μg/kg)に対する血圧上昇量のdose-response curveを2度描いた. 1)saline(n=5), 2)angiotensin II受容体遮断剤, losartan(1 mg/kg, n=6), 3)ACE阻害剤, captopril(1mg/kg, n=6), 4) bradykinin B2受容体遮断剤, Hoe 140(1 mg/kg)+captopril(1 mg/kg, n=7), 5) NO合成阻害剤, L-NAME(10 mg/kg)+captopril(1 mg/kg, n=6), 6) prostaglandin合成阻害剤, indomethacin(5 mg/kg)+captopril(1 mg/kg, n=6). ［結果］1)captoprilはNAに対する昇圧反応を抑制した. 2) losartanはNAに対する昇圧反応を抑制しなかった. 3) Hoe140の前処置はcaptoprilによるNAの昇圧抑制作用を消失せしめた. 4) L-NAMEの前処置はcaptoprilによるNAの昇圧抑制作用を消失せしめた. 5) indomethacinの前処置はcaptoprilによるNAの昇圧抑制作用に影響を与えなかった. ［結論］captoprilのnoradrenalineに対する昇圧反応の抑制は, captopril→bradykininの増加→bradykinin B2受容体の刺激→nitric oxide産生増加→noradrenalineの昇圧抑制という機序が推定され, prostaglandinの関与はないことが示唆された.
Practice基礎医学・関連科学
KeywordsCaptopril, Bradykinin B2 receptor, Nitric oxide, Prostaglandin, Noradrenaline
English
TitlePressor Response to Noradrenaline is Blocked by the Pretreatment with Captopril Through the Production of Nitric Oxide via the Activation of Bradykinin B2 Receptors
Subtitle
AuthorsShinya Minatoguchi*, Hiroyasu Ito**, Hitomi Yokoyama*, Masatoshi Koshiji*, Yoshihiro Uno*, Hisayoshi Fujiwara*
Authors(kana)
Organization*2nd Department of Internal Medicine, Gifu University School of Medicine, **Sawada Hospital
JournalCirculation Control
Volume18
Number1
Page45-50
Year/Month1997/
ArticleOriginal article
PublisherJapan Society of Circulation Control
AbstractAngiotensin-converting enzyme (ACE) inhibitors such as captopril have been widely used for the treatment of hypertension. One of the mechanisms for decreasing blood pressure has been suggested to be decreased vascular reactivity to noradrenaline (NA), but the details of this mechanism remain unknown. Herein, the aim of this study was to investigate whether nitric oxide and/or prostaglandins are involved in the decreased vascular reactivity to noradrenaline exerted by captopril. Dose-response curves for mean blood pressure in response to NA (0.1, 0.2, 0.5, 1 and 2 μg/kg, i.v.) were obtained in the pithed Sprague-Dawley rats. The first and second dose-response curves were constructed consecutively with the following drugs administered intravenously during the second curves；1) saline (n=5), 2) losartan (an angiotensin II antagonist, 1 mg/kg, n=6), 3) captopril (an ACE inhibitor, 1 mg/kg, n=6), 4) Hoe 140 (a bradykinin B2 receptor blocker, 1 mg/kg) + captopril (1 mg/kg, n=7), 5) L-NAME (an inhibitor of NO synthesis, 10 mg/kg) + captopril (1 mg/kg, n=6), 6) indomethacin (an inhibitor of prostaglandin synthesis, 5 mg/kg) + captopril (1 mg/kg, n=6) Captopril significantly decreased the pressor responses to NA. The decreased pressor responses to NA exerted by captopril was restored by the pretreatment with Hoe 140. Furthermore, the decreased pressor responses to NA exerted by captopril was also restored by the pretreatment with L-NAME, however, pretreatment with indomethacin did not affect the decreased pressor responses to NA exerted by captopril. We conclude that captopril decreases the pressor responses to NA through the bradykinin B2 receptormediated production of nitric oxide, but not through the production of prostaglandins in the pithed rat. (Circ Cont 18：45〜50, 1997)
PracticeBasic medicine
KeywordsCaptopril, Bradykinin B2 receptor, Nitric oxide, Prostaglandin, Noradrenaline

【全文PDF】