In vivo and in vitro alterations of active and inactive plasma renins in the rat.

Abstract

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

Activation by Puff Adder Venom of Inactive Renin in Normal and Hypertensive Rat Plasma

“…Moreover, the proportion of total renin that is inactive renin (62vo) was quite similar to values of 59% (Barrett et al 1982) and 60% (Doi et al 1984) calculated from data of two other groups who used trypsin for activation in rat plasma. The present work thus supports the data obtained by these groups, but does not support the high values reported by another group (Osmond et al 1982;Ioannou et al 1983) who have also reported very high values in dog plasma (Wilczynski & Osmond 1983), where artefacts have been identified when using trypsin for activation (Gallagher et al 1980).…”

“…In the case of rat plasma, 10-30-fold higher concentrations of trypsin have also been found necessary in order to obtain activation (Barrett et al 1982;Osmond el al. 1982;Glorioso et al 1983;Ioannou et al 1983;Doi et al 1984;Schiffrin et al 1984).…”

“…More recently, however, activation has been reported in rat plasma using much higher concentrations of trypsin (2-6 mg/ml). The data are, nevertheless, variable, as can be seen if one calculates the proportion of total renin that is inactive renin in the various reports (so eliminating variations in absolute levels reported using different renin assays): 38% (Glorioso et al 1983), 44% (Schiffrin et al 1984), 59% (Barrett et al 1982), 60% (Doi et al 1984), 75% (Osmond et al 1982) and 87% (Ioannou et al 1983). Thus, either activation was incomplete in at least some of these studies or the procedures employed have introduced artefacts contributing to erroneous overestimates.…”

“…It should be noted, though, that values for the quantity of inactive renin (and renin) in the literature vary. For exampleBarrett et al (1982) report basal values of -1.5 pmol AI/h per ml, whereasDoi et al (1984) find values oE -15. The values in the present study lie between these.…”

Circulating Levels of Active, Total and Inactive Renin (Prorenin), Angiotensin I and Angiotensinogen in Carbon Tetrachloride‐treated Rats

“…chronic restriction of dietary sodium) modifies in the same direction renin and prorenin (Toffelmire et al 1989). Studies in animals have shown that prorenin levels can be modified with acute stimulus and that active renin does not always change in the same direction as prorenin (Barret et al 1982;Barret & Eggena 1986;Kattan et af. 1990).…”