Circulating versus tissue renin-angiotensin system: on the origin of (pro)renin

Angiotensin synthesis at tissue sites is well established, and interference with tissue angiotensin is now believed to underlie the beneficial effects of renin-angiotensin system blockers. Initially, it was thought that the renin required to synthesize angiotensin at tissue sites was also synthesized locally. However, recent studies show this is not the case at important cardiovascular sites (eg, the heart and vessel wall). Moreover, extrarenal sites that express the renin gene release prorenin, the inactive precursor of renin, instead of renin. This review provides an update on the sources of (pro)renin in the body, lists the known stimulants and inhibitors of its production, and discusses the concept that prorenin rather than renin determines tissue angiotensin generation.