Plasma kallikrein and plasmin as activators of prorenin: links between the renin-angiotensin system and other proteolytic systems in plasma.

Renin is a circulating proteolytic enzyme acting at the physiological pH of blood; a circulating inhibitor of this enzyme has not been identified. Therefore, most studies on the biological significance of renin are based on the classical model of a circulating hormone. Renin, however; does not act on cellular receptors; it acts by virtue of its enzymatic activity. Evidence has accumulated in recent years that a proportion of the renin in human plasma has little or no enzymatic activity. About 80% of the total potential renin activity of normal plasma is in this inactive form [1-4]. Possibly we are dealing here with a proenzyme comparable with the proenzymes that are activated by limited proteolysis in important physiological processes, such as coagulation, fibrinolysis, inflammatory responses and complement-mediated reactions. Usually, these processes are initiated in close contact with the blood vessel wall and not in circulating plasma. This could also apply to the renin-angiotensin system, so that circulating renin activity is not always a good index for the biological activity of the system. The traditional endocrinologist’s view on renin is perhaps too 1 i m i t e d . Inactive renin can be separated from active renin by ion-exchange chromatography [5,61 and by affinity chromatography with pepstatin and certain dye ligands [71. As will be discussed, inactive renin is converted (activated) in vitro into an active form of renin by various pro-