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New Inhibitors of Human Renin Tested in vitro and in vivo in the Anaesthetized Baboon

 

作者: Malcolm Tree,   Butrus Atrash,   Brian Donovan,   John Gamble,   Allan Hallett,   Maria Hughes,   D Michael Jones,   Brenda Leckie,   Anthony Lever,   James Morton,   Michael Szelke,  

 

期刊: Journal of Hypertension  (OVID Available online 1983)
卷期: Volume 1, issue 4  

页码: 399-403

 

ISSN:0263-6352

 

年代: 1983

 

出版商: OVID

 

关键词: Renin inhibitor;angiotensin I;angiotensin II;blood pressure;baboons

 

数据来源: OVID

 

摘要:

A new inhibitor of human renin (H.189) is described. It is a decapeptide analogue of human renin substrate with the amino acid, statine, substituted for leucine in the scissile bond. Its inhibitory potency as shown by IC50is 1.0 x 10″6 M with human plasma renin and 1.5 x 10″8 M with baboon plasma renin. It is less effective with dog and rat renin, but its inhibitory potency with human renin is similar to that of another inhibitor of ours (H. 142) having a reduced isosfere in the scissile bond. H.189 has some inhibitory effect on cathepsin D (IC50 6.5 x 10-8M) but H.142 has no discernible effect. Pepstatin, on the other hand, was highly effective against cathepsin D (IC501.2 x 10″8 M). H.142 and H.189 were infused intravenously at 10 mg/kg/h in four anaesthetized salt-deplete baboons (Papio hamadryas). The activity of renin in plasma decreased markedly as did the circulating concentration of its products, angiotensin I and angiotensin II.

 

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