Generation of Inactive Renin in Vitro and in Vivo: Reversible Inactivation of the Active Plasma Enzyme in Rats

Abstract

1. Active and total (trypsin treatment) plasma renins were measured in normal Wistar rats and in rats in which the renin-angiotensin system was stimulated by ether anaesthesia. 2. After incubation of normal plasma in vitro in the absence of angiotensinase inhibitors, active renin declined. This decline was shown to be due to the conversion of active renin into an inactive form, which could be re-activated by trypsin. 3. In plasma from renin-stimulated rats, the rate of decline of active renin in vitro was accelerated; however, the relative amount of inactive renin generated was decreased. 4. Ligation of the kidneys of the ether-anaesthetized animal resulted in a build-up in vivo of inactive renin concomitant with the decline of active renin. 5. These data demonstrate the conversion of active into inactive renin in vitro and indicate that inactive renin can also be generated in vivo from the active form of the enzyme. 6. Multiple forms of inactive renin may exist; some may be true ‘prorenins’ (renin zymogens) produced in the kidney, and others may result from post-biosynthetic modifications of the active plasma enzyme.