Evidence for the functional significance of multiple renin forms

Our laboratory demonstrated the existence of 6 forms of renin, (F1-F6) each with a unique isoelectric point (pI). We ascribe the heterogeneity to differences in glycosylation. This heterogeneity has been demonstrated to exist in all animals studied in our laboratory, across a wide evolutionary scale. Multiple forms have been found in fish, amphibians, birds and mammals, including humans. We have been able to demonstrate that hepatic inactivation of the renin forms in humans is different for each form. Isolation and purification of the forms allowed injection of a single form into rats. IV infusion of F4 resulted in a significant natriuresis and diuresis, while the other forms had no significant renal effects. However, if the same forms were infused into the cerebroventricles at a much lower dose, F6 caused a natriuresis. Pretreatment with converting enzyme inhibitor abolished that effect. We were able to show that Spontaneously Hypertensive Rats (SHR) exhibited a renin profile that was altered in a predictable way and was significantly correlated with their blood pressure. The hepatic clearance of each form was also different, so that the forms have different half lives. These data support the hypothesis that renin heterogeneity is dependent upon glycosylation and is functionally significant.