SUMMARY The levels of active, inactive, and total renin (trypsin treatment) were measured in rat plasma before and after in vivo stimulation or suppression of active plasma renin. Stimulation of active renin was accompanied by either an increase (low sodium diet), no change (pentobarbital anesthesia plus hemorrhage), or fall (pentobarbital anesthesia) in the plasma levels of inactive renin, while suppression of active renin was accompanied by a fall (high sodium diet) or mild but nonsignificant Increases (clonldlne or saline infusion) of the inactive enzyme. These results suggest the possible independence of in vivo regulation of active and inactive renin in the rat.Trypsin However, the in vivo mechanism(s) that control the plasma levels of these enzymes has not been determined, and definitive information is not available as to whether the plasma levels of active and inactive renin can vary independently.In an attempt to determine whether alterations of active plasma renin can be related to changes in inactive renin, we used several antihypertensive agents and alterations in sodium diet to either stimulate or suppress active plasma renin. In addition, we fractionated plasma by isoelectric focusing techniques to determine: 1) which of the five isoelectrically distinct forms of active plasma renin 5 is altered following changes of active plasma renin; and 2) the isoelectric focusing distribution of plasma renins(s) that can be activated by trypsin. We used the rat as an experimental model since previous studies from this laboratory have indicated that rat plasma is a rich source of inactive renin as measured by both acid dialysis* and trypsin treatment.
MethodsWistar Kyoto rats, bred in our laboratory, weighing from 150 to 200 g, were used for this study. Experimental diets were given for 2 weeks, consisting of Ralston Purina with a high sodium content (3.15% Na + ) and saline (0.9%) as drinking fluid, or with a low sodium content (0.05% Na + ) and distilled water as drinking fluid. Metolazone (5.0 mg/kg/day, s.q.), chlorthalidone (12.5 mg/liter drinking water), propranolol (320 mg/liter drinking water), and clonidine (280 ^g/liter drinking water) were also given for a period of 2 weeks with a normal sodium diet. The average daily water intake was approximately 30 ml per animal. A minimum of 10 animals was included in each study group. Animals were sacrificed by cervical dislocation, and blood was obtained from the left ven