Kinetic Analysis of the Reaction of Human Renin with Human High and Low Molecular Weight Angiotensinogen

Abstract

Objective: In addition to the usual predominant form of plasma angioten-sinogen (low molecular weight angiotensinogen) (LM_rA) that has been well characterized, a high molecular weight form of angiotensinogen (HM_rA) occurs in appreciable quantities in plasma of pregnant women and is the predominant form of angiotensinogen in the placenta and amniotic fluid. One half of women who have pregnancy-induced hypertension exhibit significantly elevated plasma HM_rA levels. The present study is designed to determine if HM_rA is a good substrate for human renin.

Methods: The pH profile, a K_m to V for the reaction of human renin with LM_rA and HM_rA. was determined.

Results: The pH profiles for HM_rA and LM_rA were distinctly different. The experimentally determined kinetic parameters show that at pH 5.9, renin would hydrolyze both substrates at equal rates in an equimolar mixture of the two substrates at any concentration of substrate. At pH 7.3 LM_rA would be consumed 1.9 times faster than HM_rA.

Conclusions: HM_rA is a good substrate for human renin. HM_rA should be considered a significant component of the renin-angiotensin system at those sites where it occurs in an appreciable concentration. Since the concentration of LM_rA in plasma is slightly lower than the K_m for the reaction of human rennin with LM_rA, the concentration of LM_rA is a rate-limiting factor in the production of angiotensin I and angiotensin II.

Key Words:

• Angiotensinogen
• High molecular weight angiotensinogen