Total Plasma Renin Concentration Research Articles

Total renin after gonadotropin stimulation in polycystic ovarian disease

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Pathophysiological significance of plasma total renin and prorenin in patients with diabetes mellitus.

To seek the pathophysiologic significance of measuring the concentration of total renin instead of prorenin, we determined the plasma total renin concentration by immunoradiometric assay and correlated the results with various clinical features and laboratory parameters of diabetic complication in 108 patients with diabetes mellitus. The plasma prorenin concentration was estimated as the difference between the total and active renin concentrations. The plasma total renin and prorenin concentrations were high in patients with diabetes mellitus, in contrast to the active renin concentration which was slightly decreased. In addition, the plasma total renin and prorenin concentrations were higher in patients with diabetic complications than in patients without any complication. Multiple regression analysis showed that the presence of orthostatic hypotension, diabetic retinopathy, and proteinuria is significantly associated with the increased plasma total renin and prorenin concentrations. In addition, there was a significant positive correlation between the total renin and prorenin concentrations. These results suggest that both the plasma total renin concentration and the prorenin concentration are closely related to diabetic complications. Determination of the plasma total renin concentration by immunoradiometric assay as a substitute for prorenin could be a powerful tool in elucidating the mechanism for the increased plasma prorenin in diabetes mellitus.

Characterization of a Radioimmunoassay to Determine Plasma Total Renin

The determination of plasma total renin is useful not only as a tool to investigate the physiology of hypertension but also as a marker for Wilms' tumor. A radioimmunoassay (RIA) system to determine plasma total renin was newly developed using monoclonal antibodies specific for both inactive and active renin (inactive + active = total); in this study, an effort was made to confirm that this RIA system truly determines plasma total renin concentrations. First, it was found that this monoclonal antibody stains only the juxtaglomerular apparatus of the kidney. Second, the data determined by the RIA were compared with those obtained by the conventional enzymatic method: samples were activated, and renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by this RIA system and by the conventional method was 0.921 (p less than 0.01) based on all 89 samples, and 0.809 (p less than 0.01) based on 86 of the 89 samples whose values were less than 600 pg/ml by RIA. As a result of these studies, it was concluded that the newly developed RIA system does determine total renin levels in patients' plasma.

Studies on the human ovarian renin-angiotensin system: optimization of assay methodology and effects of follicular stimulants

The renal and genital tracts share a common embryological origin; it is thus not surprising that tissues from both can synthesize renin. Preliminary studies showed extremely high concentrations of renin in follicular fluid (FRC) following ovarian stimulation for in-vitro fertilization. This necessitated complete revalidation of the renin assays and showed that data obtained using commercial kits were invalid. An assay protocol was developed using a 1:2 dilution of follicular fluid taken into EDTA (0.3 mol/l) and o-phenanthroline (0.05 mol/l). The assay was performed at pH 7.5 in the presence of excess exogenous (sheep) renin substrate, with incubation periods of 5, 10 and 15 min at 37 degrees C. This protocol resulted in the linear generation of angiotensin I (AI). Activation of inactive renin was performed using eightfold more trypsin than was required for plasma samples. Follicular renin substrate concentrations (FRS) were measured using the same assay methodology as used for measurement of plasma renin substrate concentrations (PRS). Storage of samples at -18 degrees C for up to 2 months was found not to affect the FRC, although repeated freeze-thaw cycles did. FRC and plasma renin concentrations (PRC) were very similar in 25 unstimulated control women, studied in the follicular phase of the menstrual cycle. Trypsin activation increased follicular total renin concentration (FTRC) more than plasma total renin concentration (PTRC) (P less than 0.0001). FRS was slightly higher than PRS (P less than 0.02). Ovarian stimulation with clomiphene citrate (CC; six women) was without effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of the Kidney in Activation and Release of Plasma Inactive Renin in the Rat

Plasma inactive as well as active renin is supposed to originate from the kidney, though there is little direct evidence. As we have previously reported (Sakanaka et al., Folia Endocrinol. Jap., 63: 961-977, 1987; Miyazaki et al., J. Hypertension 4 (Suppl 6): S453-S455, 1986; Miyazaki et al., J. Hypertension 6: 33-40, 1988), the submandibular gland, but not the kidney, is thought to play an crucial role in releasing plasma inactive renin in the rat. In the present acute studies, we attempted to elucidate the roles of the kidney in the release mechanisms of plasma inactive renin. Adult male rats maintained on a regular rat chow (Na: 260 mg/100g) were uninephrectomized, and vessel clips were placed on the renal pedicles of the contralateral kidneys to make completely ischemic and non-filtered kidneys. In the first protocol, the renal pedicles were occluded for 2 h, followed by the removal of the vessel clips. During the occlusion for 2 h, plasma active renin concentration (PAC) in the peripheral blood obtained from the femoral cannulae decreased, while plasma inactive renin concentration (PIC) along with plasma total renin concentration (PTC) increased as in the case of total nephrectomy, which supports our previous studies. Then, declipping resulted in the rapid rise in PAC with the peak values at 2 min, which was followed by its gradual decrease with time during the experimental period (30 min). On the other hand, PIC decreased gradually toward control levels with no rise after declipping. In the second protocol, blood trapped in the kidney was collected through the renal venous cannulae at 0, 60, 120 and 240 min after the pedicle occlusion in the different groups of rats. The renal blood levels of PAC increased by more than three times at 240 min compared to the control values, while PIC decreased to one third of the control values. PTC increased at 120 and 240 min. Renal tissue levels of renin were also measured at 0 and 120 min in the second protocol in the kidneys of rats which were maintained on a regular rat chow. Inactive renin concentration increased, while active renin concentration decreased. These were compatible with the results obtained in plasma. In the last protocol, the second protocol was in part repeated in salt-depleted rats which were kept on a low salt diet (Na: 11.3 mg/100g) for 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Determination of Plasma Total Renin Concentration as a Marker for Wilms' Tumor : Value of RIA With a Monoclonal Antibody

Determination of Plasma Total Renin Concentration as a Marker for Wilms' Tumor : Value of RIA With a Monoclonal Antibody

Arterial Hypertension as a Paraneoplastic Phenomenon in Hepatocellular Carcinoma

Three South African blacks with hepatocellular carcinoma and arterial hypertension are described. Plasma angiotensinogen (renin substrate) concentrations were increased eightfold to 10-fold in the two patients in whom these concentrations were measured. One of these two patients also showed a 34-fold rise in plasma inactive, active, and total renin concentrations, and an elevated plasma renin activity (2.73 ng.L-1.s-1 angiotensin l/mL/h). Inactive renin (prorenin) constituted 90% of the total plasma renin concentration. In the third patient only plasma renin activity was measured, and this was considerably raised (6.05 ng.L-1.s-1; angiotensin l/mL/h). Thus, the arterial hypertension that rarely complicates hepatocellular carcinoma may be caused either by a combination of eutopic synthesis of excessive quantities of angiotensinogen and ectopic production and secretion of active renin by malignant hepatocytes, or by eutopic production of angiotensinogen alone.

Effects of aging on human plasma renin: simultaneous multiple assays of enzyme activity and immunoactivity of plasma renin

The effects of aging on plasma renin in normotensive volunteers were evaluated by conventional indirect RIA of angiotensin I and a newly developed direct RIA. Plasma renin activity and the plasma concentration of active renin measured by radiometric assay with monoclonal antibody were significantly lower in 14 subjects over 60 years than in 15 subjects under 60 years (plasma renin activity: 0.5 +/- 0.1 vs 1.7 +/- 0.4 nmol.1-1.h-1, P less than 0.01; plasma active renin: 0.50 +/- 0.05 vs 0.87 +/- 0.13 pmol/l, P less than 0.01, means +/- SEM), whereas neither the total renin activity nor the total plasma renin concentration measured by the newly developed immunometric assay were different in the two groups. In another study, the plasma renin concentration, total renin concentration and immunoreactive total renin concentration measured by direct RIA with polyclonal antibody were determined in 17 young (less than 60 years) and 12 elderly (greater than or equal to 60 years) subjects. Plasma renin concentration was significantly lower in the elderly subjects (1.7 +/- 0.2 nmol.l-1.h-1) than in young subjects (3.2 +/- 0.7 nmol.l-1.h-3, P less than 0.05), but the total renin concentration and immunoreactive total renin concentrations in the two groups were not significantly different. These results indicate that the total renin content of the plasma does not change, whereas the active renin content decreases with age in normal subjects, and suggest that activation of prorenin to active renin may be impaired in elderly subjects.

The renin-angiotensin-aldosterone system in normal 85-year-old people

Active and total plasma renin concentration, as well as plasma angiotensin II, aldosterone and renin substrate concentrations were measured in venous blood samples from 17 normal 85-year-old people at rest. No discernible sex-related differences were seen. Active plasma renin and plasma aldosterone concentrations were significantly lower in the old people compared to a group of normal 40-year-old people. Plasma angiotensin II concentration showed no decrease with increasing age. Active plasma renin concentration constituted approximately 20% of total plasma renin concentration, with a significant correlation between the two renin moieties. The values for plasma renin substrate concentration are similar to those reported for younger age groups. The lack of standardization of methods severely hampers inter-laboratory comparisons of both active plasma renin and total plasma renin concentrations.

Stress-induced activation of inactive renin. Molecular weight aspects.

We have investigated the response of plasma renin activity (PRA), total, active, and inactive plasma renin concentration (PRC) to immobilization stress in rats. A great increase of PRA was already found after 5 min of immobilization. In contrast, total PRC was elevated only after 1 h of stress. During the initial 15 min, the increase of active PRC was quantitatively matched by the decrease of inactive PRC. This suggests that the initial very rapid response of the plasma renin-angiotensin system to immobilization stress is facilitated by the activation of inactive renin. To get more information about this in vivo activation process, we performed gel filtration of control, acid-treated control, and plasma from 15-min immobilized rats. In the control plasma, two peaks with renin-like activity corresponded to molecular weights of approximately 43,000 and 36,000. Acid-activatable renin was eluted at four molecular weights: 50,000, 58,000, 72,000, and 85,000. In acid-treated control plasma, the peak at 85,000 was decreased and the peak at 43,000 was increased. In plasma from 15-min immobilized rats, the inactive renin of Mr 50,000 was suppressed more than that of 85,000 while the level of active renin, Mr 43,000, was much higher than in controls. The results indicate that stress-induced in vivo activation of inactive renin does not proceed by the same mechanism as in vitro acid-activation.

Role of various vasodepressor systems in the acute hypotensive effect of captopril in man.

The acute hypotensive effect of captopril 25 mg was investigated in 26 hypertensive patients (11 with essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril led to an increase in plasma renin activity, active and total plasma renin concentration and angiotensin I, a decrease in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2 alpha and no change in plasma (nor) adrenaline, dopamine and inactive renin concentration. The hypotensive effect of captopril was related to the changes in plasma angiotensin II level and inversely to the changes in prostaglandin E2; the correlation coefficients were low, respectively 0.61 and -0.44. It is likely that the acute hypotensive effect of captopril to some extent is related to changes in plasma angiotensin II and in prostaglandins E2 and F2 alpha. There is no evidence for a role of the adrenergic systems in the hypotensive response.

Biological significance of active and inactive renin in man.

The biological significance of active and inactive renin was investigated by comparison of an in-vitro assay of active, total and inactive plasma renin concentration (PRC), plasma renin activity (PRA) and plasma concentrations of angiotensin I and II with an in-vivo change in mean arterial blood pressure (MAP) produced by antagonism of angiotensin with treatment with saralasin and by blockade of angiotensin-converting enzyme by treatment with captopril. A significant relationship between the changes in MAP during treatment with saralasin and captopril with the pretreatment levels of PRA, active and total PRC and angiotensin II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During treatment with saralasin and captopril significant increases in PRA, plasma angiotensin I concentration and total and active PRC were found and no change in inactive PRC was observed.

A Renal Carcinoma Secreting Inactive Renin

1. A patient presented with mild hypertension, a raised plasma total renin concentration but a normal plasma angiotensin II concentration. The discrepancy was due to a high concentration of inactive renin in the plasma. 2. A renal carcinoma was detected and removed. The tumour contained a higher proportion of inactive renin than was found in uninvolved areas of the kidney. After unilateral nephrectomy, the plasma concentration of inactive renin fell to normal. 3. Six months later, plasma inactive renin concentration again increased and a metastasis was detected in a rib. Excision of the rib together with radiotherapy resulted in a fall in plasma inactive renin to normal. 4. The inactive renin in plasma and tumour extracts was activated to the same extent by acid treatment and by trypsin.

Measurement of renin concentration in human plasma using 125I-labelled sheep renin substrate

Sheep renin substrate was prepared 28% pure, labelled with 125I and then diluted in concentrated unlabelled sheep substrate. Ten percent of the 125I-label was released as a small fragment on incubation with excess human renin. Adequate separation of the labelled fragment from the parent protein was accomplished with charcoal precipitation or gel filtration. Renin concentration in human plasma was assayed by incubating the 125I-labelled substrate with plasma under zero-order kinetic conditions. Renin was assayed in plasma that had been either acidified or untreated. The acidification procedure was employed to activate inactive renin which accounted for more than half of the total plasma renin concentration. The results of this radiochemical assay correlated closely with the results of bioassay. Specificity of the method was established with antirenin. The assay was sufficiently sensitive to measure suppressed plasma renin levels. The iodinated substrate was stable on storage at −10°C over a six-month period. Because of its high affinity for human renin, ease of purification and stability of the iodinated product, sheep substrate provides a convenient means for routine determination of plasma renin concentration by radiochemical assay.