Linking the kallikrein and renin systems via activation of inactive renin. New data and a hypothesis

An inactive form of renin occurs in normal plasma and in various diseases in amounts capable of generating much more renin than is generally present in active form. The inactive renin-like material in plasma seems largely, but not completely, of renal origin and can be converted to an active renin-like substance in vitro by either acid or cold treatment. These observations are of considerable practical relevance for improving routine renin measurements since certain methods which acidify plasma have inadvertently measured both inactive and active renin. Avoidance of chilling during collection of blood will also improve the precision of renin measurements. A series of observations has demonstrated that both acid- and cryoactivation of inactive plasma renin are enzymatic processes involving a neutral serine protease. Characterization of these in vitro activation processes has led to the demonstration that an intrarenal enzyme with similar biochemical characteristics, urinary kallikrein, is an extremely powerful activator of inactive renin. In view of the location of this enzyme, adjacent to renin in the kidneys, it seems possible that it may function physiologically to trigger the renin system. In the light of these findings a hypothesis has been proposed to explain the coordinated control of systemic pressure and local tissue flow in which renal kallikrein may activate the renin system which, in turn, releases angiotensin II to maintain or defend systemic arterial pressure. Concurrently, the kallikrein-kinin system would function within the kidney to maintain local tissue flow in the face of angiotensin-induced systemic vasoconstriction. In this construction kinins are not viewed as circulating hormones. More research is needed to test this hypothesis and to work out the steps involved in its organization.