Functional relevance of the microheterogeneity of active renin

We previously demonstrated the presence of six active forms of renin in rats, based on their isoelectric points (pI). Intravenous or intraventricular injections yielded different renal effects with the different forms. Additional work is presented supporting the hypothesis that these forms are functionally different. Renin form 2 (pI = 5.7), form 4 (pI = 5.2) or form 6 (pI = 4.8) was infused intravenously (IV) in Spague-Dawley rats. The total renin infused over 30 minutes was the amount that could generate 1000 ng angiotensin I (Ang I)/h/100g body weight. Arterial blood pressure, urine volume, sodium, and potassium excretion were determined at 15-minute intervals. Plasma renin activity (PRA) and plasma aldosterone concentrations were measured 45 minutes after the start of infusion of renin forms. Infusion of renin form 4 increased urine volume and sodium excretion significantly. Renin forms 2 and 6 were without effect on renal excretion in spite of the fact that the same activity was infused. Both PRA and aldosterone concentrations after renin infusions were similar for all groups. Nonrenin renal protein with the same pI as form 4 was used as a control. This preparation was inactive and implies that our data with renin form 4 were not the result of contamination with a nonrenin protein having a pI of 5.2. In addition, the urinary responses could not be attributable to change in renal perfusion pressure as arterial blood pressure was not altered. These data support the hypothesis that there are functional differences among the different renin forms.