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Kokyu to Junkan Volume 33, Issue 6 （June 1985）

呼吸と循環 33巻6号（1985年6月発行）

Japanese English

研究

MK-421（enalapril）の急性降圧効果とrenin-angiotensin系，kallikrein-kinin系に及ぼす影響 Acute effect of MK-421(enalapril) on blood pressure, the renin-angiotensin system and the kallikrein-kinin system in hypertensive patients 近藤宏一 ¹ , 木田修 ¹ , 児玉健二 ¹ , 比嘉利信 ¹ , 染谷典行 ¹ , 諸冨康行 ¹ , 田仲謙次郎 ¹ Koichi Kondo ¹ , Osamu Kida ¹ , Kenji Kodama ¹ , Toshinobu Higa ¹ , Noriyuki Someya ¹ , Yasuyuki Morotomi ¹ , Kenjiro Tanaka ¹ ¹宮崎医科大学第一内科 ¹The First Department of Internal Medicine, Miyazaki Medical College pp.811-815

発行日 1985年6月15日 Published Date 1985/6/15

DOI https://doi.org/10.11477/mf.1404204696

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Abstract 文献概要
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　1976年，angiotensin I変換酵素阻害剤のcaptoprilが最初に経口的に臨床応用可能になり^1），この2,3年の間に高血圧の成因の分析又は治療目的にangiotensin I変換酵素（ACE）を阻害することが臨床的，実験的に有効な手段であることがわかってきた^2,3）。降圧剤としてのcaptoprilの評価は高いが，反面，発熱・掻痒感・味覚異常などの副作用^4〜6），まれに白血球減少^7）が報告されており，問題がないわけではない。しかもその副作用はSH基を有するpenicillamineのそれと類似していることから^8），このSH基を除去することにより副作用を軽減できるのではないかという可能性が示唆された。MK-421（enalapril）はSHを持たない新しいangiotensin I変換酵素阻害剤（CEI）であり^9），著明な降圧効果，とくにその効果の持続性が諸家により報告されている^9〜12）。今回，われわれは各種高血圧症に対し，このMK-421の1回経口投与における急性降圧効果と，renin-angioten—sin系（R-A系），kallikrein-kinin系（K-K系）に及ぼす影響について検討した。

Acute effects of a new converting enzyme inhib-itor, MK-421, on renin-angiotensin and kallikrein-kinin systems were examined in twelve hypertensive subjects.

They were included five patients with essential hypertension, four patients with renovascular hypertension and three hypertensives with renal parenchymal disease, and their mean age was 46.3 years. All antihypertensive drugs had been discon-tinued at least two weeks, and then 5mg of MK-421 given orally under normal sodium diet intake. Supine blood pressure and pulse rate were contin-uously monitored every 5 minutes before and 1, 2, 3, 4, 8. 12 and 24 hours after administration. Samples of blood were withdrawn before and 1, 4 and 24 hours after, and renin activity, aldcsterone concentration and bradykinin in plasma (PRA, PAC and BK) were measured by radioimmunoassay.

Blood pressure was maximally reduced from 154 ±6/98±3 mmHg to 124±7/81±4 mmHg (mean±SE, P<0.001) at 12 hours, and was significantly reduced even at 24 hours later. While, pulse rate remained unchanged in any time. PRA and BK were maximally increased from 3.5±0.7 ng/ml/h to 5.52±1.1 ng/ml/h (P<0.01) at 4 hours and from 27.0±8.2 pg/ml to 42.7±6.9 pg/ml (P<0.05) at 1 hour, respectively. And PAC was significantly decreased from 143.1±18.7 pg/ml to 106.0±13.2 pg/ml (P< 0.01) at 4 hours. The maximal fall in mean blood pressure was correlated with not only pretreatment level of PRA (r=-0.62, P<0.05) but also that of BK (r=-0.733, P<0.05).

It is concluded that MK-421 is a potent convert-ing enzyme inhibitor whose action lasts for over 24 hours. And its antihypertensive effect might appear to be closely linked to inhibition of BK degradation as well as angiotensin II synthesis.