Effects of sodium depletion on inactive and active renin from dog kidney and plasma.

Abstract

SUMMARY The relationship of active renin and inactive renin (trypsin-activated angiotensin-I-forming enzyme) to sodium depletion was examined in renal and peripheral plasma and at the subcellular level in the kidneys of dogs. Subcellular fractionation was carried out by discontinuous sucrose density (1.5 and 1.6 M) centrifugation. Sodium depletion selectively caused a six-to sevenfold increase in the renal content of inactive and active renins in the original homogenate, while the subcellular distribution patterns of these enzymes were little changed. Of the total granule fractions of 1.5 M sucrose (Fl), 1.6 M sucrose (F2), and sediment (F3), approximately 80% of inactive renin was recovered in Fl, which was rich in microsomes, while about 50% of active renin was in F2. The ratio of inactive to active renin was 0.02 in Fl and 0.003 to 0.004 in F2. Sodium depletion also caused a 20-fold increase in active renin and a twofold increase in inactive renin in peripheral plasma. The renal venous-arterial concentration difference of inactive renin was statistically significant in lowsodium dogs, although it was not significant in controls. The ratio of inactive to active renin was 0.2 to 0.4 in plasma from low-sodium dogs, while it was 1.5 to 3 in plasma from control dogs. These results suggest that plasma inactive renin originates, at least in part, in the kidney. T is now widely accepted that human plasma contains an inactive form of renin, which can be activated with trypsin. 1 -2 However, little is known of the physiological mechanisms controlling the activation of inactive renin. Recently, inactive renin was detected in human kidney extracts 3 " 5 and also in the renin granules.6 Plasma inactive renin is thought to originate, at least to some extent, in the kidney, although an extrarenal origin has also been suggested. "9 In laboratory experiments, inactive renin was detected in dog 10 and rat"-l2 plasma and dog 10 and hog 13 kidneys. It is well known that plasma active renin usually reflects the active renin content of the kidney. In particular, sodium intake is a major determinant in con- trolling the active renin in plasma and kidney. 1415However, only limited information exists on the responses of inactive renin to sodium depletion in both the plasma and kidney. As renin is known to be synthesized in a precursor form in the microsomal fraction, 16 the inactive renin content of the kidney should aiso be examined at subcellular levels. Therefore, we have evaluated the effect of sodium restriction on renin concentration of renal and peripheral plasma and on subcellular distribution of kidney renin. Material and Methods Experimental ProtocolSixteen male mongrel dogs weighing 18 to 20 kg were kept in metabolic-balance cages and given tap water ad libitum. For over 2 weeks before the study, the animals were fed a standard laboratory dog chow (Japan Clea Company, Osaka, Japan) containing 57.5 mEq sodium and 88 mEq potassium per daily intake. Each daily urine collection was analyzed for sodium and potassium contents. A...

The storage form of renin in renin granules from rat kidney cortex.

“…On the other hand, we found that inactive renin constitutes 20% of total renin activity (active renin + inactive renin) in human renin granules 9 and 0.3% in dog renin granules. 22 We also found inactive renin in microsomal fractions in rat kidney (unpublished observation). Thus, conversion of inactive to active renin during maturation of renin granules appears to be more rapid in dogs and rats than in humans.…”

“…Trypsin treatment was performed as reported previously. 22 To remove active renin, 5 ml of sample was applied to a pepstatin Sepharose column. The pass-through fraction was concentrated to 5 ml, and the aliquot was incubated with trypsin (100 /Ag/ml) up to 60 minutes.…”