INHIBITION OF HUMAN RENIN BY RAT PLASMA - RAT ANGIOTENSINOGEN IS A COMPETITIVE INHIBITOR OF THE HUMAN RENIN-SUBSTRATE INTERACTION

被引：5

作者：

GAHNEM, F ^{[1
]}

SEALEY, JE ^{[1
]}

ATLAS, SA ^{[1
]}

LARAGH, JH ^{[1
]}

机构：

[1] CORNELL UNIV,MED CTR,NEW YORK HOSP,COLL MED,CTR CARDIOVASC,525 E 68TH ST,NEW YORK,NY 10021

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1992年 / 5卷 / 08期

关键词：

HUMAN RENIN; RAT ANGIOTENSINOGEN; HUMAN ANGIOTENSINOGEN; RENIN SUBSTRATE REACTION RATE; MICHAELIS-MENTEN CONSTANT; ANGIOTENSIN GENERATION RATE;

D O I：

10.1093/ajh/5.8.495

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Human renin can cleave rat angiotensinogen, yet infusion of human renin into rats causes only a modest increase in blood pressure. We therefore investigated whether there is a factor in rat plasma which inhibits human renin activity. The addition of 20% normal rat plasma to human plasma had a slight, but not significant, inhibitory effect on the rate of angiotensin formation, while nephrectomized rat plasma, which had a seven-fold higher concentration of angiotensinogen, caused a dose dependent inhibition (20 to 70%). The rat plasma inhibitor copurified with angiotensinogen. Analysis of the kinetics of the human renin-human substrate reaction and of the human renin-rat substrate reaction revealed that the rate of angiotensin I production in the presence of both substrates could be entirely accounted for by assuming that rat and human angiotensinogens are competitive inhibitors of each other. These results show that human renin can cleave rat substrate but the reaction rate is extremely slow relative to the cleavage of human angiotensinogen. They also indicate that rat angiotensinogen is an effective competitive inhibitor of the human renin-substrate reaction. These results may be relevant to the development of renin inhibitors and to transfection studies involving heterologous renin or substrate genes.

引用

页码：495 / 501

页数：7

共 21 条

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