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(Hypertension. 2006;48:549.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Prorenin and Its Ancient Receptor

Céline Burcklé; Michael Bader

From the Max Delbrück Center for Molecular Medicine, Berlin, Germany.

Correspondence to Michael Bader, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str 10, D-13092 Berlin-Buch, Germany. E-mail mbader@mdc-berlin.de

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Prorenin, the precursor of renin, has for a long time been considered to be functionally inert, despite high circulating concentrations. Plasma levels of prorenin usually exceed renin levels and are even further increased under pathological conditions, such as in diabetes. First support of a functional significance of prorenin came from studies in transgenic rats, which overexpress a renin gene in the liver resulting in high circulating prorenin levels.¹ Without systemic renin–angiotensin system activation and with normal blood pressure, these animals developed a vascular phenotype reminiscent of malignant hypertension. Moreover, in a series of elegant experiments, Ichihara et al^2–4 supported the concept of prorenin as a relevant factor in the pathophysiology of diseases, such as hypertension and diabetes, by using a peptide that binds and inhibits the activation of the precursor. Thus, this peptide attenuated nephropathy in streptozotocin-induced diabetes² and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.³ By successfully repeating the streptozotocin experiment in mice deficient for the angiotensin II type 1a (AT_1a) receptor, they reported recently that these effects are independent of renin activation or angiotensin II generation and concluded that the peptide, in fact, inhibits the interaction of prorenin with a receptor.⁴

In this issue of Hypertension, Saris et al⁵ contribute further evidence for an angiotensin-independent action of prorenin on cells by showing that neonatal cardiomyocytes respond to purified prorenin by p38 mitogen-activated protein (MAP) kinase phosphorylation and broad changes in gene expression partially also caused by the MAP kinase activation. Because the authors had shown before . . . [Full Text of this Article]

Related Article:

Prorenin Induces Intracellular Signaling in Cardiomyocytes Independently of Angiotensin II

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