Hypertension in the (mRen-2)27 rat is not explained by enhanced kinetics of transgenic Ren-2 renin.
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.
D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D013045:Species Specificity
C473112:Ren2 protein, mouse; D000808:Angiotensinogen; D012083:Renin