Alternative routes for angiotensin-I conversion: kinetics of the renin-angiotensin system in mouse plasma

Angiotensin-I in plasma may be converted to angiotensin-II or alternatively metabolized through other routes. The aim of the present work has been to quantitate the role of the alternative routes in mouse plasma. A kinetic model for metabolism of the angiotensins through the renin-angiotensin system is proposed, the model allows for alternative routes and for simultaneous reactions to occur. Exogenously added angiotensin-I and angiotensin-II, or endogenously formed angiotensin-I and angiotensin-II from the action of exogenously added renin, were measured in plasma with time. The concentrations of angiotensin-I and angiotensin-II were measured by radioimmunoassay after separation by Dowex cation exchange and HPLC reverse-phase chromatography. The rate constants for the enzymatic reactions were experimentally determined and fitted to the kinetic model. The data were incompatible with a quantitative conversion of angiotensin-I to angiotensin-II, and indicate that about half of the angiotensin-I formed in plasma is metabolized in plasma through alternative routes.