Big renin in plasma of healthy subjects on high sodium intake

Normal human plasma contains not only active renin but also an inactive form of renin which, after exposure to low pH, can generate angiotensin I from renin substrate. When healthy volunteers were given first a diet containing 400 mmol sodium and then a diet containing 10 mmol sodium for 4 days the changes in salt intake stimulated large changes in active plasma-renin and smaller changes in inactive renin. Inactive renin comprises a larger fraction of total renin in plasma of salt-loaded healthy subjects than salt depleted subjects. When plasma of healthy men on a high-salt diet was applied to a column of 'Sephadex G-100', renin eluted in two peaks, corresponding to big renin (60 000 daltons) and normal renin of lower molecular weight (40 000 daltons). Active and inactive forms of renin were present in both peaks. Plasma from salt depleted healthy subjects showed a large single peak of renin activity with a maximum at 40 000 daltons. These studies demonstrate that both big and small renin can exist as inactive or active enzyme. Big renin, previously found in certain diseases and in pregnancy, is also present in normal human plasma. These observations suggest a possible physiological role for big renin.