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.

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.

scholarly journals Renal vein plasma renin activity in patients with essential hypertension and renovascular hypertension.

1986 ◽  
Vol 75 (6) ◽  
pp. 728-732
Author(s):  
Ko SATO ◽  
Keishi ABE ◽  
Masahide SEINO ◽  
Minoru YASUJIMA ◽  
Yutaka IMAI ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Plasma Renin Activity ◽  
Renovascular Hypertension ◽  
Renal Vein ◽  
Plasma Renin ◽  
Renin Activity

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.

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.

Two-Site Direct Immunoassay Specific for Active Renin

1992 ◽  
Vol 38 (10) ◽  
pp. 1959-1962 ◽  
Author(s):  
D Simon ◽  
D J Hartmann ◽  
G Badouaille ◽  
G Caillot ◽  
T T Guyenne ◽  
...  
Keyword(s):  
Magnetic Beads ◽  
Active Form ◽  
Plasma Renin ◽  
Active Plasma ◽  
Immunoradiometric Assay ◽  
Active Renin ◽  
Human Renin ◽  
Direct Immunoassay ◽  
Inactive Renin ◽  
Normotensive Subjects

Abstract A sensitive immunoradiometric assay, without an enzymatic step and specific for active human renin, was developed with use of two monoclonal antibodies (MAbs). In this assay system, the first MAb was coupled to magnetic beads (Magnogel); the second one, directed against the active form of the enzyme, was radiolabeled with 125I. The specificity of this assay was demonstrated in experiments measuring the active plasma renin concentration in the presence or absence of inactive renin. The assay, performed in two steps, was sensitive enough to detect 0.9 pg of renin per tube (3.5 ng/L). Intra- or interassay CVs were &lt; 10%. Concentrations of active plasma renin measured in normotensive subjects were between 7 and 40 ng/L.

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.

Divided Renal and Peripheral Venous Renin as a Means of Predicting Operative Curability of Renal Hypertension

1973 ◽  
Vol 45 (s1) ◽  
pp. 311s-314s ◽  
Author(s):  
Kikuo Arakawa ◽  
Zenziro Masaki ◽  
Yukio Osada ◽  
Junko Yamada ◽  
Shunro Momose
Keyword(s):  
Plasma Renin Activity ◽  
Similar Pattern ◽  
Renal Vein ◽  
Renal Hypertension ◽  
Plasma Renin ◽  
Arterial Stenosis ◽  
Lateral Side ◽  
Corrective Surgery ◽  
Parenchymal Lesion ◽  
Affected Side

1. Eighteen patients with unilateral arterial stenosis or renal parenchymal lesion underwent corrective surgery for hypertension. Operative curability of hypertension was compared with pre-operative plasma renin activity (PRA) determined in three different veins; affected side renal (A), contralateral renal (C), and peripheral veins (P). 2. Those with renal arterial stenosis in whom the PRA in the affected side renal vein was significantly higher (more than 14 ng/ml) than that in both the contra-lateral side and peripheral veins, i.e. those with PRA values showing a pattern of A > C=P were found surgically curable without exception. 3. Patients with unilateral renoparenchymal lesions showed either A, C > P or A = C=P pattern and these were all found not curable. A similar pattern was found in four controls.

Orthostatic Changes of Haemodynamics, Renal Function, Plasma Catecholamines and Plasma Renin Concentration in Normal and Hypertensive Man

1972 ◽  
Vol 42 (2) ◽  
pp. 209-222 ◽  
Author(s):  
M. Molzahn ◽  
TH. Dissmann ◽  
S. Halim ◽  
F. W. Lohmann ◽  
W. Oelkers
Keyword(s):  
Essential Hypertension ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renovascular Hypertension ◽  
Negative Correlation ◽  
Positive Relationship ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Filtration Fraction ◽  
Plasma Renin Concentration

1. In eight normal subjects, ten patients with labile hypertension, six with advanced essential hypertension and six with renovascular hypertension, plasma renin concentration, cardiac output, mean arterial pressure, clearances of creatinine and p-aminohippurate (PAH), and sodium excretion were measured before and after 30 min of 45° upright tilting. Changes in plasma adrenaline and noradrenaline concentration were measured in addition in the normal subjects, and in plasma volume in normal subjects and patients with labile essential hypertension. 2. In patients with advanced essential hypertension, heart rate and calculated peripheral resistance increased significantly less than in normal subjects, and plasma renin increased by 15% in this group, in comparison to 37% in normal subjects, 48% in labile essential hypertension, and 57% in renovascular hypertension. There was a positive relationship between changes in renin and noradrenaline concentrations in normal subjects. 3. Apart from a negative correlation between the increases in plasma renin concentration and mean arterial pressure in patients with renovascular hypertension, there were no significant relationships between changes in plasma renin and haemodynamics. 4. A negative correlation between changes in plasma renin and filtration fraction and a positive relationship between changes in renin and sodium excretion were found in normal subjects and patients with labile hypertension. Plasma renin increase was directly related to changes in the tubular rejection fraction of sodium in patients with labile hypertension. In the same group there was a negative correlation between changes of sodium rejection fraction and filtration fraction. 5. The results suggest a role of the adrenergic system in orthostatic renin release, but the functional connection between renal haemodynamics, tubular sodium handling and renin release across orthostasis cannot fully be explained on the basis of our present knowledge of renin releasing mechanisms.

Acute Effects of Captopril on Blood Pressure and Circulating Hormone Levels in Salt-Replete and Depleted Normal Subjects and Essential Hypertensive Patients

1981 ◽  
Vol 61 (1) ◽  
pp. 75-83 ◽  
Author(s):  
J. A. Millar ◽  
B. P. McGrath ◽  
P. G. Matthews ◽  
C. I. Johnston
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Pulse Rate ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Primary Role ◽  
Ang Ii ◽  
Acute Effects ◽  
Mean Values ◽  
Plasma Renin Concentration

1. The acute effects of a single oral dose of captopril on blood pressure, pulse rate and circulating levels of angiotensin I (ANG I), angiotensin II (ANG II), renin, bradykinin and catecholamines were studied in three groups: eight normal subjects, six salt-depleted normal subjects and 16 patients with essential hypertension. 2. Captopril treatment did not cause any significant fall in supine blood pressure in salt-replete normal subjects or patients with untreated essential hypertension but was associated with a fall in mean blood pressure from 85 ± 2 to 75 ± 2 mmHg in salt-depleted normal subjects and from 131 ± 7 to 117 ± 5 mmHg in patients with essential hypertension treated with diuretics. There was no change in pulse rate in any group. 3. Hormonal responses to captopril were qualitatively similar in the three groups and consisted of significant falls in ANG II with corresponding increases in ANG I and plasma renin concentration. The changes in plasma renin concentration and ANG I were greater in salt-depleted normal subjects (mean values at 90 min were 1140% and 990% of basal levels respectively) than in salt-replete normal subjects (410%, 190%) and were blunted in patients with essential hypertension (140%, 120%). Blood bradykinin, noradrenaline and adrenaline concentrations did not change after captopril in any group. 4. The parallel fall in blood pressure and ANG II levels in salt-depleted normal subjects is consistent with maintenance of blood pressure by increased levels of ANG II in sodium depletion. 5. The failure of captopril to reduce acutely blood pressure in patients with essential hypertension despite suppression of plasma ANG II and without change in circulating bradykinin confirms that the renin-angiotensin system does not play a primary role in essential hypertension.

The cat: an animal model for studies of inactive renin

1987 ◽  
Vol 252 (4) ◽  
pp. E509-E518
Author(s):  
N. Glorioso ◽  
C. Troffa ◽  
J. H. Laragh ◽  
S. A. Atlas ◽  
D. Marion ◽  
...  
Keyword(s):  
Animal Model ◽  
Human Plasma ◽  
Plasma Renin ◽  
Renin Inhibitor ◽  
Adrenergic Blockade ◽  
Sodium Depletion ◽  
Ph Optimum ◽  
Active Renin ◽  
Inactive Renin ◽  
High Concentrations

Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin.

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