Evidence for Activation of Circulating Inactive Renin by the Human Kidney

1979 ◽  
Vol 56 (2) ◽  
pp. 115-120 ◽  
Author(s):  
F. H. M. Derkx ◽  
G. J. Wenting ◽  
A. J. Man In't Veld ◽  
R. P. Verhoeven ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Renal Vein ◽  
Human Kidney ◽  
Activation Process ◽  
Peripheral Vein ◽  
Active Renin ◽  
A Value ◽  
Before And After ◽  
Inactive Renin ◽  
Propranolol Treatment ◽  
Stimulation Of

1. In eight patients with essential hypertension (EHT) and six patients with renovascular hypertension (RVHT) peripheral venous enzymatically active and inactive renin values were followed after acute stimulation of renin release by the vasodilating agent diazoxide (300 mg intravenously). Active renin rose during the first hour after diazoxide and remained high during the following 15 h, but inactive renin fell during the first hour and rose thereafter. Peripheral venous active and inactive renin were not different from arterial values both before and after diazoxide. 2. Sixteen patients with EHT received propranolol, 80 mg, four times a day. Six of them had a first injection of diazoxide the day before propranolol was started and a second one after 10–14 days of propranolol treatment. Peripheral vein active renin was lowered by propranolol, but inactive renin was raised. Both the diazoxide-induced rapid rise of active renin and the fall of inactive renin observed in untreated patients were absent during treatment with propranolol. 3. In four patients with EHT and seven patients with RVHT renal vein sampling was performed before and 30 min after diazoxide. Increased release of active renin from kidneys that were not markedly contracted was associated with a fall of the renal vein to peripheral vein ratio of inactive renin to a value less than one. 4. It is concluded that under certain circumstances stimulated release of active renin is associated with removal of inactive renin from the circulation by the kidney. This may in fact be due to intrarenal transformation of circulating inactive renin into its active counterpart. The findings suggest that a β-adrenoreceptor might be involved in this activation process.

Renal Release of Active and Inactive Renin in Essential and Renovascular Hypertension

1978 ◽  
Vol 55 (s4) ◽  
pp. 129s-132s ◽  
Author(s):  
F. H. M. Derkx ◽  
R. P. Verhoeven ◽  
G. J. Wenting ◽  
A. J. Man in 't Veld ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Essential Hypertension ◽  
Renovascular Hypertension ◽  
Intravenous Injection ◽  
Renal Vein ◽  
Active Renin ◽  
A Value ◽  
Affected Side ◽  
Inactive Renin ◽  
Arterial Plasma

1. Active and acid-activable inactive renin were measured in renal venous and arterial plasma of 18 patients with essential hypertension (EHT) and 19 patients with renovascular hypertension (RVHT). In seven patients with EHT and in 11 patients with RVHT measurements were made before and 25–35 min after an intravenous injection of 300 mg of diazoxide. 2. Under basal conditions the renal vein to artery ratios for active and inactive renin in EHT ranged from 0·71 to 1·96 and from 0·68 to 1·44 respectively. In 14 patients with RVHT the renal vein to artery ratio for active renin on the affected side was above the range found in EHT and in six of them the renal vein to artery ratio for inactive renin was also elevated. 3. The diazoxide-induced release of active renin from kidneys, which had a stenotic artery but were not seriously contracted, was associated with a fall of the renal vein to artery ratio for inactive renin to a value below 1·00. 4. The results indicate that changes in the release of active and inactive renin do not always run in parallel. The findings are compatible with the hypothesis that circulating inactive renin can be activated in the kidney.

Renin Secretion by the Human Kidney

1978 ◽  
Vol 55 (s4) ◽  
pp. 147s-149s
Author(s):  
W. H. Birkenhäger ◽  
P. W. De Leeuw ◽  
H. E. Falke ◽  
G. A. W. Van Soest
Keyword(s):  
Blood Flow ◽  
Active Form ◽  
Human Kidney ◽  
Blood Samples ◽  
Active Renin ◽  
Intrarenal Blood Flow ◽  
Inactive Renin ◽  
Propranolol Treatment ◽  
Xenon Washout

1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies. 2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout. 3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.

Control of Enzymatically Inactive Renin in man under Various Pathological Conditions: Implications for the Interpretation of Renin Measurements in Peripheral and Renal Venous Plasma

1978 ◽  
Vol 54 (5) ◽  
pp. 529-538 ◽  
Author(s):  
F. H. M. Derkx ◽  
G. J. Wenting ◽  
A. J. Man In 'T Veld ◽  
R. P. Verhoeven ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Essential Hypertension ◽  
Renovascular Hypertension ◽  
Renal Vein ◽  
Plasma Renin ◽  
Peripheral Vein ◽  
Native Form ◽  
Mean Values ◽  
Active Renin ◽  
Affected Side ◽  
Inactive Renin

1. Human plasma contains two types of renin: one is active in its native form (active renin), the other has renin-like activity after exposure to low pH (inactive renin). Reactions of acid-activated plasma renin and kidney renin with either homologous or heterologous substrate showed identical Km values. 2. Peripheral venous values for active and inactive renin in essential hypertension (n = 22), renovascular hypertension (n = 14), primary aldosteronism (n = 12), adrenal insufficiency (n = 6) and control subjects (n = 13) were directly correlated. But the percentage of renin that was active varied widely. 3. After bilateral nephrectomy in 12 patients both active and inactive plasma renin fell, but did not completely disappear. Estimates of half-life in two patients were 30–80 min for active renin and 150–165 min for inactive renin. 4. Renal vein to peripheral vein ratios of active and inactive renin in ten patients with essential hypertension (19 determinations) ranged from 0·96 to 1·60 and from 0·68 to 1·44 respectively with mean values (±sem) of 1·21 ± 0·04 and 1·06 ± 0·05. 5. The renal vein to peripheral vein ratio of active renin on the affected side in 13 out of 17 patients with renovascular hypertension was above the range found in essential hypertension. Six of them also had an elevated ratio of inactive renin on that side, which indicated renal release of this form of renin into the circulation. But, in contrast to the renal vein to peripheral vein ratio of active renin, the mean value of the ratio of inactive renin on the affected side was not significantly higher than on the contralateral side. The results suggest a renal mechanism not only for controlling the total quantity of circulating renin but also for modulating its degree of activation.

Noradrenaline Secretion by the Human Kidney

1978 ◽  
Vol 55 (s4) ◽  
pp. 85s-87s ◽  
Author(s):  
P. W. De Leeuw ◽  
H. E. Falke ◽  
R. Punt ◽  
W. H. Birkenhäger
Keyword(s):  
Blood Flow ◽  
Human Kidney ◽  
Treated Group ◽  
Blood Samples ◽  
Hypertensive Patients ◽  
Active Renin ◽  
Noradrenaline Secretion ◽  
Propranolol Treatment ◽  
Arteriovenous Difference ◽  
Xenon Washout

1. In 20 subjects with uncomplicated essential hypertension, 10 of whom were on propranolol treatment, several blood samples were drawn simultaneously from the renal artery and vein after angiographic studies. In these samples we determined concentrations of noradrenaline, active renin, aldosterone and cortisol. 2. Renal blood flow was measured in all patients by Hippuran-clearance and xenon-washout. 3. Despite marked variations in the arteriovenous difference of noradrenaline, it was apparent in both groups that the kidney is able to release noradrenaline. 4. In the propranolol-treated group noradrenaline secretion by the kidney was enhanced when compared with untreated hypertensive patients.

Active and Inactive Renin in Individual Juxtaglomerular Apparatuses

1980 ◽  
Vol 59 (s6) ◽  
pp. 35s-36s
Author(s):  
A. Gillies ◽  
T. Morgan ◽  
W. Fitzgibbon
Keyword(s):  
Salt Intake ◽  
Active Form ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Active Renin ◽  
High Salt Intake ◽  
Before And After ◽  
Inactive Renin ◽  
Inhibitor Of Protein Synthesis

1. Renin was measured in individual juxtaglomerular apparatuses before and after acidification in vitro.. 2. Active renin increased with delivery of extra sodium by microperfusion to the macula densa and this increase was similar to that achieved with acidification. 3. In rats pretreated with an inhibitor of protein synthesis active renin increased when extra sodium was delivered to the macula densa. 4. Salt intake changed the amount of renin present in the juxtaglomerular apparatus. In rats on a high salt intake the total renin was low and was all in an active form.

Active and inactive renin in primary and secondary adrenal insufficiency and during ACTH infusion

1983 ◽  
Vol 102 (2) ◽  
pp. 265-270
Author(s):  
Lutz Belkien ◽  
Petra Exner ◽  
Wolfgang Oelkers
Keyword(s):  
Plasma Renin ◽  
Renal Secretion ◽  
Young Males ◽  
Active Renin ◽  
Group I ◽  
Inactive Renin ◽  
Group Ii ◽  
Peripheral Activation ◽  
The Relationship ◽  
Stimulation Of

Abstract. Prolonged low-dose ACTH infusion leads to a transient stimulation of plasma renin activity (PRA) and angiotensin II. In part 1 of the present study (infusion of 10 IU of ACTH per day for 38 h into 6 normal young males), it was shown that the concentration of active renin (aPRC) increases in parallel to PRA. Thus, the rise in PRA is either due to net active renin secretion by the kidney or to increased conversion of inactive into active renin. Since the plasma concentration of inactive renin (iPRC) tended to rise rather than to fall during ACTH infusion, peripheral activation of inactive renin is probably not the cause of the rise in aPRC. Part 2 of the study consisted in the measurement of plasma ACTH, cortisol, PRA, aPRC and iPRC in 10 patients (group I) with primary adrenocortical insufficiency (8 Addisonians, 2 adrenalectomized Cushing's) and in 9 patients with hypopituitarism (group II) after short-term withdrawal of hydrocortisone substition therapy. ACTH was 1770 ± 390 pg/ml in the former and 20 ± 4 pg/ml in the latter group. PRA and aPRC were higher and the ratio iPRC:aPRC lower in group I than in group II. This might indicate stimulation of active renin formation by ACTH. However, it is unlikely that the higher aPRC levels in group I are due to increased peripheral activation of inactive renin, since the relationship between aPRC and the ratio iPRC:aPRC fell on the same curve in both groups. ACTH or an ACTH-dependent mechanism raises aPRC, probably by stimulating its renal secretion rather than by peripheral activation of inactive renin.

Uptake of Inactive Renin by Human Ischaemic Kidney

1983 ◽  
Vol 65 (1) ◽  
pp. 27-32 ◽  
Author(s):  
I. M. McKenzie ◽  
E. Reisin ◽  
J. K. McKenzie
Keyword(s):  
Essential Hypertension ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Peripheral Blood ◽  
Renal Vein ◽  
Vena Cava ◽  
Artery Stenosis ◽  
Renal Ischaemia ◽  
Active Renin ◽  
Inactive Renin

1. Plasma samples from both renal veins and infrarenal inferior vena cava were studied in 21 patients with unilateral renal artery stenosis and 11 patients without significant renal artery stenosis (essential hypertension), both groups being on unrestricted sodium intake. 2. Whether inactive renin was activated by acid or trypsin, it tended to be increased by 50–100% in unilateral renal ischaemia patients compared with essential hypertension. Active renin was increased two- to four-fold in unilateral renal ischaemia patients compared with those with essential hypertension. Thus the ratio of active to total renin in peripheral venous blood tended to be higher in unilateral renal ischaemia (0.37) than in essential hypertension (0.30) patients. 3. in renal vein blood from the affected kidney in unilateral renal ischaemia, the proportion of active renin to total renin was very high (68% for trypsinized samples and 73% for acidified samples). When affected renal vein blood was compared with infrarenal vena caval blood (equivalent to renal artery blood in amount and proportions of active and inactive renin), there was found to be a marked increase of active renin (ratio 2.83, significance of difference from 1.0, P < 0.001), as expected. 4. Inactive renin was decreased in affected renal vein blood compared with peripheral blood (ratio of renal vein to peripheral blood renin). This occurred whether acidification was used (ratio 0.62 ±0.11, P < 0.01) or trypsin (ratio 0.70 ± 0.13, P < 0.05). 5. The cause of the apparent uptake may be conversion of inactive renin into active renin by protease action in the ischaemic kidney. Urinary excretion or lymphatic drainage would seem unlikely.

Stimulation of plasma inactive renin by dexamethasone in the cat

1989 ◽  
Vol 257 (6) ◽  
pp. E879-E884
Author(s):  
N. Glorioso ◽  
C. Troffa ◽  
G. Tonolo ◽  
M. G. Melis ◽  
P. Manunta ◽  
...  
Keyword(s):  
Time Course ◽  
Consensus Sequence ◽  
Recovery Period ◽  
Base Line ◽  
Active Renin ◽  
Human Renin ◽  
Inactive Form ◽  
Inactive Renin ◽  
Selective Increase ◽  
Stimulation Of

An inactive form of renin in human plasma is the biosynthetic precursor, prorenin. The cat is a good animal model for studies of inactive renin. The gene for human renin contains sequences homologous to the glucocorticoid consensus sequence. The response of cat plasma (active and inactive renin) and of angiotensinogen to administration of dexamethasone (0.5 mg/kg im, daily) was studied in ketamine-sedated cats (20 mg/kg im). Inactive renin increased by twofold after 7 days of dexamethasone (P less than 0.01). After a 7-day recovery period, it returned to base line. Active renin did not change. Angiotensinogen fell by 35% (P less than 0.01). The time course of the selective increase of plasma inactive renin showed that inactive renin began to rise after 2 days, peaking after 5 days. Ketamine alone induced inactive renin to rise slightly but significantly (P less than 0.05), although the magnitude of the increment was much less than that observed in ketamine-sedated cats receiving dexamethasone (P less than 0.01). Active renin did not change, whereas angiotensinogen was reduced by 25% (P less than 0.01). Our findings support the hypothesis that glucocorticoids might have a selective role in the synthesis and/or secretion of the precursor of renin, at least in the cat.

Potential effects of renin activation on the regulation of renin production

1984 ◽  
Vol 247 (2) ◽  
pp. F205-F212 ◽  
Author(s):  
W. A. Hsueh
Keyword(s):  
Cdna Probe ◽  
Human Kidney ◽  
Adrenergic System ◽  
Diabetic Patients ◽  
Beta Adrenergic ◽  
Active Renin ◽  
Human Renin ◽  
Release Studies ◽  
Normal Humans ◽  
Inactive Renin

In normal humans nearly half the renin in plasma and kidney is inactive. Human inactive renin can be activated by a variety of proteases and by exposure to low pH and is a putative biosynthetic precursor of renin, i.e., prorenin. Pulse-labeling studies in a human renin-secreting tumor suggest that renin is synthesized as a prepro- and proform, both of which are inactive. Using the cDNA probe to deduce the amino acid sequence of precursor renin from the nucleotide sequence of human kidney mRNA, the prosegment was estimated to be 46 amino acids long, similar to differences in molecular weight between active and inactive renin. In plasma of diabetic patients with nephropathy and the syndrome of hyporeninemic hypoaldosteronism, inactive renin levels are increased 3-5 times normal. The inability to activate renin in this syndrome strongly implies that conversion of inactive (pro-) renin to active renin may be physiologically relevant to active renin production. Furthermore, in normal humans profound stimulation of active renin can be accompanied by a reciprocal drop in circulating inactive renin levels. The beta-adrenergic system and prostaglandins are two major, but independent, mechanisms of stimulating renin release. Studies in our laboratory suggest that prostaglandins and the beta-adrenergic system may act at different sites in renin production: beta-stimulation may act at early steps in renin biosynthesis, while prostaglandins may act preferentially at later steps that possibly involve conversion of inactive to active renin. Proof of this hypothesis lies in purification of inactive renin to determine whether it is prorenin and in the use of the renin cDNA probe to study pre- vs. posttranslational events in renin processing.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Reduction in Inactive Renin after Stimulation of Active Renin by Converting Enzyme Inhibition (CEI) in Man

1982 ◽  
Vol 63 (s8) ◽  
pp. 175s-177s ◽  
Author(s):  
W. A. Hsueh ◽  
R. Goldstone ◽  
E. J. Carlson ◽  
R. Horton
Keyword(s):  
Single Dose ◽  
Salt Intake ◽  
Repeated Administration ◽  
Active Renin ◽  
Low Salt ◽  
Inactive Renin ◽  
Converting Enzyme Inhibition ◽  
Normal Man ◽  
Circulating Levels ◽  
Stimulation Of

1. Administration of a single dose of captopril, 50 mg, to normal man (n = 7) on a low salt intake induced a 12.5 ± 0.9-fold rise in active renin. The rise in active renin was associated with a reciprocal decrease in circulating inactive renin to 10% or less of control levels. 2. Repeated administration of captopril (50 mg p.o. q 6 h × 3 days) to normal man resulted in increases in both active and inactive renin concentration in plasma. 3. When a single dose of captopril was administered to three patients with hyporeninaemic hypoaldosteronism, no changes in their circulating levels of active or inactive renin occurred. 4. These observations suggest that renal conversion of inactive to active renin may be important in active renin production.

Sign in / Sign up

Export Citation Format

Share Document