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(Hypertension. 2006;47:824.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Prorenin

Back Into the Arena

A.H. Jan Danser

From the Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands.

Correspondence to Dr A.H.J. Danser, Department of Pharmacology, Rm EE1418b, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: a.danser@erasmusmc.nl

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

Prorenin, the precursor of renin, exists in circulating blood at concentrations that are 5 to 10x higher than those of renin. For many years, prorenin was considered to be an inactive form of renin with no physiological role. Then, in the mid-80s of the last century, Luetscher et al reported that the levels of circulating prorenin (but not renin) are increased in diabetic subjects.¹ Subsequent studies revealed that these high levels correlated with the presence of microvascular complications, and it was proposed that prorenin might be used to predict the occurrence of microalbuminuria.² Simultaneously, high prorenin levels were observed in pregnant women, and evidence was obtained for the local synthesis of prorenin at extrarenal tissue sites such as the ovary and eye. Until today, however, the exact function of prorenin remains unknown.

An attractive concept is that in tissues not synthesizing renin locally, circulating prorenin, after its local conversion to renin, contributes to angiotensin (Ang) generation. This would not only provide a role for prorenin in vivo, but also explain why tissues, in contrast with plasma, contain predominantly renin.³ Studies in transgenic animals support this idea. Véniant et al⁴ described that transgenic rats expressing prorenin exclusively in the liver (resulting in a 400-fold rise in plasma prorenin) display cardiac hypertrophy and vascular damage in the absence of hypertension. Prescott et al⁵ detected increased cardiac Ang I levels in mice overexpressing human prorenin in the liver and human angiotensinogen in the heart.

The question then arises how tissues sequester and . . . [Full Text of this Article]

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