HALF-LIFE, HEMODYNAMIC, RENAL, AND HORMONAL EFFECTS OF PRORENIN IN CYNOMOLGUS MONKEYS

被引:52
作者
LENZ, T
SEALEY, JE
MAACK, T
JAMES, GD
HEINRIKSON, RL
MARION, D
LARAGH, JH
机构
[1] CORNELL UNIV, MED CTR,COLL MED,CTR CARDIOVASC,DEPT PHYSIOL, 525 E 68TH ST, NEW YORK, NY 10021 USA
[2] CORNELL UNIV, MED CTR,COLL MED,DEPT UROL, NEW YORK, NY 10021 USA
[3] UPJOHN CO, DEPT BIOCHEM, KALAMAZOO, MI 49001 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1991年 / 260卷 / 04期
关键词
HUMAN RECOMBINANT PRORENIN; PHARMACOKINETICS; RENAL FUNCTION; ANGIOTENSIN-II; ALDOSTERONE; TESTOSTERONE; BLOOD PRESSURE; RENIN;
D O I
10.1152/ajpregu.1991.260.4.R804
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20-mu-g; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P < 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P < 0.001). Heart rate, glomerular filtration rae, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-mu-g doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P < 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P < 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.
引用
收藏
页码:R804 / R810
页数:7
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