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(Hypertension. 1999;33:312-317.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Human Prorenin in Rats Transgenic for Human Angiotensinogen

Dominik N. Müller; Karl F. Hilgers; Salima Mathews; Volker Breu; Walter Fischli; Regina Uhlmann; Friedrich C. Luft

From the Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin (D.N.M., R.U., F.C.L.) and the University of Erlangen-Nürnberg (K.F.H.), Germany; and Hoffmann-La Roche (S.M., V.B.) and Actelion (W.F.), Basel, Switzerland.

Correspondence to Friedrich C. Luft, MD, Franz Volhard Clinic, Wiltberg Strasse 50, 13122 Berlin, Germany. E-mail luft{at}fvk-berlin.de

Abstract—The physiological role of prorenin is unknown; however, the possibility that prorenin inhibits renin locally has been suggested. We tested the hypothesis that prorenin may be an endogenous competitor for renin uptake in the tissue. We also investigated whether prorenin can be activated to active renin 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 minutes after cessation of infusions was used as a parameter for renin uptake. Renin (10 ng/mL for 15 minutes) caused sustained release of Ang I (153±16 fmol/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 activation to active renin. In addition, we investigated MAP and plasma Ang II levels after injection of saline (MAP, -1±2 mm Hg; 40±5 fmol/mL Ang II), 9 ng renin (MAP, +37±3 mm Hg; 378±39 fmol/mL), and 144 ng prorenin (MAP, +10±5 mm Hg; 61±5 fmol/mL) and the coinjection of renin and prorenin (MAP, +41±4 mm Hg; 305±23 fmol/mL) in anesthetized rats. The data show that prorenin was not activated to active renin and did not affect MAP in short-term experiments. Renin-induced Ang formation was not affected by prorenin. Renin may have been taken up specifically because of its physical and chemical properties or because of nonspecific sequestration in the extravascular space. We conclude that prorenin does not act as an endogenous antagonist for the long-lasting effects of renin in the vascular wall. Moreover, prorenin does not affect acute renin-related effects on blood pressure.

Key Words: rats, transgenic • angiotensinogen • angiotensin • prorenin • renin • hindlimbs

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