Effects of human prorenin in rats transgenic for human angiotensinogen

The physiological role of prorenin is unknown; however, the possibility tha t prorenin inhibits renin locally has been suggested. We tested the hypothe sis that prorenin may be an endogenous competitor for renin uptake in the t issue. We also investigated whether prorenin can be activated to active ren in and affect mean arterial pressure (MAP), Isolated perfused hindquarters of rats transgenic for human angiotensinogen were infused with human renin and/or prorenin. The plateau phase of angiotensin (Ang) I release 15 minute s after cessation of infusions was used as a parameter for renin uptake, Re nin (10 ng/mL for 15 minutes) caused sustained release of Ang I (153+/-16 f mol/mL). Coinfusion with a 15-fold excess of prorenin did not affect local Ang I formation (153+/-19 fmol/ml). Prorenin infusion alone showed no activ ation to active renin. In addition, we investigated MAP and plasma Ang II l evels after injection of saline (Delta MAP, -1+/-2 mm Hg; 40+/-5 fmol/ml An g II), 9 ng renin (Delta MAP, +37+/-3 mm Hg; 378+/-39 fmol/mL), and 144 ng prorenin (Delta MAP, +10+/-5 mm Hg; 61+/-5 fmol/ml) and the coinjection of renin and prorenin (Delta MAP, +41+/-4 mm Hg; 305+/-23 fmol/mL) in anesthet ized rats. The data show that prorenin was not activated to active renin an d did not affect MAP in short-term experiments. Renin-induced Ang formation was not affected by prorenin. Renin may have been taken up specifically be cause of its physical and chemical properties or because of nonspecific seq uestration in the extravascular space, We conclude that prorenin does not a ct as an endogenous antagonist for the long-lasting effects of renin in the vascular wall. Moreover, prorenin does not affect acute renin-related effe cts on blood pressure.