Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin

Abstract

Enhanced efficiency of the reaction between transgenic Ren-2 mouse renin and endogenous rat angiotensinogen has been suggested as 1 mechanism that contributes to the accelerated hypertension and increased tissue angiotensin of the (mRen-2)27 transgenic rat. This was tested in a study conducted at pH 7.4 in vitro that compared the kinetic constants of purified mouse Ren-2 and rat renin (each at 100, 75, 50, and 25 pmol/L) reacting with physiologic concentrations of rat angiotensinogen (0 to 4 micromol/L). Under these conditions, the kinetic constants for Ren-2 (Km, 1.8 micromol/L; Kcat, 0.07/s; and Kcat/Km, 0.04 L x micromol(-1) x s(-1)) were not different from rat renin. However, Ren-2 renin acting on its homologous mouse angiotensinogen was confirmed as being much slower. We conclude that hypertension in the Ren-2 rat is not related to renin kinetics. Other mechanisms are considered, with reference to human essential hypertension.