Total Renin Research Articles

Prorenin secretion from human placenta perfused in vitro

We examined whether renin (prorenin plus renin) is secreted from the human placenta into the maternal or fetal circulation and compared the secretion rate to that of human chorionic gonadotropin (hCG), progesterone, and estradiol. While estradiol and progesterone passed into both circulations, renin (mostly prorenin) and hCG were secreted predominantly into the maternal circulation. To examine if prorenin passed from the maternal to the fetal circulation and vice versa, we perfused both circuits separately with exogenous recombinant human prorenin. No prorenin passed from maternal to fetal circulations, but a small amount (less than 10%) slowly passed from fetal to maternal, beginning 15 min after the addition of prorenin. Exogenous prorenin was not converted to renin in either circulation. Perfusate total renin had close to 10% active renin, whereas that of tissue extracts was closer to 50%. In conclusion, the results are consistent with some tissue activation of prorenin, either in vitro or in vivo, but no activation in the maternal or fetal circulations. The human placenta may secrete prorenin into the maternal but not into the fetal circulation. The possibility that the placenta may secrete a small amount of active renin into the maternal circulation was not ruled out.

Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus monkeys

Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20 micrograms; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P less than 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P less than 0.001). Heart rate, glomerular filtration rate, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-micrograms doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P less than 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P less than 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.

Age-Dependent Differences in Active and Inactive Renin in the Lamb Fetus

Most studies examining the developmental aspects of renin secretion in fetal lambs have focused on measurements of active renin. Data from these studies demonstrated age-dependent differences in renin release in vivo and in vitro. However, little information is available concerning gestational changes in total (active and inactive) renin. Therefore, we have measured the renin concentration in plasma, amniotic fluid and various tissues before and after trypsin treatment (for total renin) using 7 fetuses at 0.61-0.79 gestation (immature) and 7 fetuses at 0.88-0.97 gestation (mature). We found that active and total renin levels in plasma and kidney tissues were significantly lower in immature than in mature fetuses, while inactive renin levels were not different. We also found that the amniotic fluid, the adrenal gland, the placenta and membranes all contained low levels of active and total renin that were not different between groups. These results suggest that, over the last third of gestation, maturation influences the regulation of active renin in the kidney and plasma. The data also indicate that the renin concentration in the amniotic fluid, the adrenals, the placenta and membranes is regulated differently than that in the plasma and the kidney.

The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin

Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradiometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non-renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the renin-angiotensin-aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome.

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.

Effect of Cyproterone Acetate on Active and Inactive Renin Secretion in Patients with Precocious Puberty and Genetic Short Stature

To evaluate the effect of cyproterone acetate (CA) on the renin-angiotensin-aldosterone axis, we measured the plasma active, inactive and total renin concentrations (PARC, PIRC and PTRC) during and after CA treatment in patients with precocious puberty and genetic short stature. CA was administered at a daily dose of 150-170 mg/m2 in all subjects. PARC and PTRC were measured by immunoradiometric assays. During CA treatment, PARC, PIRC, PTRC and the PARC/PTRC ratio were significantly decreased. The plasma renin activity, measured by enzymatic assay, and the plasma aldosterone concentration were also decreased. After CA discontinuation, all of these were increased immediately along normal ranges. PARC closely correlated with plasma renin activity. These results suggest that CA produces mineralocorticoid action and suppresses the production and activation of renin.

A Targeting Sequence for Dense Secretory Granules Resides in the Active Renin Protein Moiety of Human Preprorenin

Human renin plays an important role in blood pressure homeostasis and is secreted in a regulated manner from the juxtaglomerular apparatus of the kidney in response to various physiological stimuli. Many aspects of the regulated release of renin (including accurate processing of prorenin to renin, subcellular targeting of renin to dense secretory granules, and regulated release of active renin) can be reproduced in mouse pituitary AtT-20 cells transfected with a human preprorenin expression vector. Using protein engineering, we have attempted to define the roles of various structures in prorenin that affect its production and trafficking to dense core secretory granules, resulting in its activation and regulated secretion. Replacement of the native signal peptide of human preprorenin with that of a constitutively secreted protein (immunoglobulin M) had no apparent effect on either the constitutive secretion of prorenin or the regulated secretion of active renin in transfected AtT-20 cells. Removal of the pro segment resulted in a marked reduction in total renin secretion, but did not prevent renin from entering the regulated secretory pathway. Single or combined mutations in the two glycosylation sites of human renin did not prevent its regulated secretion; however, the complete elimination of glycosylation resulted in a significant increase in the ratio of renin/prorenin secreted by the transfected cells. Thus, these results suggest that 1) at least one of the sequences that target human renin to dense secretory granules lies within the protein moiety of active renin; 2) the presence of the pro segment is important for efficient prorenin and renin production; and 3) glycosylation can quantitatively affect the proportion of active renin secreted.

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)

Circadian Variations of Total Renin, Active Renin, Plasma Renin Activity and Plasma Aldosterone in Clinically Healthy Young Subjects

The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Time-qualified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span.

Stimulation of Active Renin Release in Normal and Hypertensive Pregnancy

1. Active plasma renin concentration but not total renin concentration is reduced in women with pregnancy-induced hypertension compared with normotensive pregnant women. This study was conducted to determine whether women with pregnancy-induced hypertension are able to stimulate release of active renin. 2. Active plasma renin concentration was measured as the generation of angiotensin I at physiological pH in the presence of excess renin substrate, and total renin concentration was determined in the same way after trypsin activation. Inactive plasma renin concentration was calculated as the difference between total renin and active plasma renin concentrations. 3. Resting active plasma renin concentration was significantly greater in third-trimester primigravidae compared with normotensive non-pregnant women and active plasma renin and total renin concentrations rose significantly without a fall in inactive plasma renin concentration in both groups after 2 h ambulation, suggesting increased release of active plasma renin and not conversion of circulating inactive to active renin. These responses were blunted in women taking oral contraceptives. 4. Although the active plasma renin concentration was significantly reduced in third-trimester primigravidae with pregnancy-induced hypertension, total renin concentration was not significantly different compared with normotensive women of similar gestation and in both groups 30 min 60 degrees head-up tilt increased active but not inactive plasma renin concentration. 5. These studies show that in normal pregnancy active plasma renin concentration can be stimulated to a similar extent as in non-pregnant women, despite a higher resting level. This appears to be due to increased secretion of active plasma renin rather than conversion of circulating inactive to active renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered synthesis of renin in patients with insulin-dependent diabetes: plasma prorenin as a marker predicting the evolution of nephropathy

Plasma active renin (PARC) and plasma total renin (PTRC) were measured in 72 patients with childhood-onset IDDM and 37 control subjects in the supine posture. The diabetic patients were divided into three groups: group A, 55 patients with normoalbuminuria; group B, 11 patients with microalbuminuria; and group C, 6 patients with overt proteinuria. The levels of PTRC were 125 ± 51, 240 ± 124 and 580 ± 285 ng/l in groups A, B and C, respectively; all of which were significantly higher than 114 ± 33 ng/l in the control subjects. On the other hand, the ratios of plasma active to total renin, ARC/TRC, were 18.1 ± 12.5, 10.7 ± 6.7, and 2.9 ± 1.4% in groups A, B and C, respectively; all of which were in turn significantly lower than 24.8 ± 8.7% in the control subjects. Among the diabetic groups, PTRC became higher and ARC/TRC became lower in conjunction with the degree of albuminuria. The acute increments of PARC and PTRC during a standing load test were subsequently observed in 7 patients of group A, 5 of group B, 4 of group C, 13 patients with non-diabetic glomerulonephritis, and 6 control subjects. The ratios of increments of PARC to that of PTRC, ΔARC ΔTRC , were 48.3 ± 22.3, 35.1 ± 10.4 and 8.4 ± 8.1% in groups A, B, C, respectively; all of which were significantly lower than 84.2 ± 48.6% in the control subjects. Patients with non-diabetic glomerulonephritis showed, to a lesser degree, low ratio of ΔARC ΔTRC (60.4 ± 37.9%) in conjunction with higher level of PTRC (249 ± 89 ng/l). This level of PTRC was significantly higher than 116 ± 29 in the control subjects and 170 ± 64 ng/l in group A. The levels of PARC were relatively maintained until overt diabetic nephropathy occurred. These findings suggest that patients with IDDM may have an altered synthesis of renin with the lowered conversion rate of prorenin to the active one as early as in the normoalbuminuric stage. Although the mechanism of high PTRC and low ARC/TRC in diabetic nephropathy may relate to the glomerular hyperfiltration through chronic activation of tubuloglomerular feedback loop, the precise events remain to be clarified. We propose a prospective study to see whether ARC/TRC along with PTRC can be a functional marker predicting the evolution of diabetic nephropathy.

Determination of plasma total renin level by RIA with a monoclonal antibody: Value as a marker for nephroblastoma

Plasma total renin is a new, useful marker for nephroblastoma, but the conventional method for determining its level is sophisticated and requires large blood samples. To develop a simpler technique, a monoclonal antibody specific for both inactive and active renin (inactive + active = total) was raised, and a radioimmunoassay (RIA) system was established. This monoclonal antibody stains only the juxtaglomerular apparatus; values determined by this RIA did not change before and after activation. So far, the RIA system has been applied to 136 samples from 92 patients. Plasma total renin levels were also determined with the conventional method: samples were activated, then renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by these two different techniques was 0.921 ( P < .01). Plasma total renin levels in patients with nephroblastoma were significantly increased (546.5 ± 297.8 pg/mL) over those in patients with neuroblastoma (218.6 ± 46.5 pg/mL) and in controls (165.8 ± 67.5 pg/mL, P < .01). After removal of Wilms' tumors, the levels decreased to normal when sampled every 2 weeks. It was concluded that a newly developed RIA system is more useful in determining plasma total renin levels in patients with nephroblastoma.

Measurement of renin secretion in single perfused rabbit glomeruli

A new technique is presented that allows the measurement of the renin secretion rate of single rabbit glomeruli during in vitro perfusion at controlled afferent arteriolar perfusion pressure. Rabbit glomeruli with intact afferent arteriole and Bowman's capsule are obtained by microdissection and cannulated with a pipette system that allows continuous afferent arteriolar pressure measurement. The renin secretion rate of 10 glomeruli, perfused at 40 mmHg, was measured in 15-min intervals with an antibody-trapping microassay. Renin secretion rate was low relative to total renin content (1.2-2.0% of content/perfusion h) and increased three- to fivefold in response to isoproterenol (10(-5) M). The afferent arteriole contracted to norepinephrine (10(-5) M) in each instance. This novel, although difficult, technique allows the study of renin release in vitro at controlled perfusion pressure, without the interfering effects of the macula densa, arterial angiotensin II, and the adrenergic nervous system. It should allow a new perspective on issues such as the pressure-flow dependence of renin release and the interaction of the afferent arteriolar endothelium with the renin-secreting juxtaglomerular cells.

Follicular fluid renin concentration and IVF outcome

Total renin protein concentration (TRC) was measured in stored follicular fluid (FF) samples from 42 women. Samples were selected according to their origin from follicles either without recovered ova ('empty', n = 38) or fertilized but with failed implantation ('failed', n = 36) or successful deliveries ('deliveries', n = 71). Ratios of number of embryos transferred to number of infants delivered were 2:1, 3:1 or 4:2 but 1:1 was not available. Non-parametric testing was applied to FF-TRC, volume and outcome. TRC was significantly higher in the delivery than the failed (P = 0.001) or empty (P = 0.002) categories. Assuming that the range of renin in failed follicles can identify the sub-population of unsuccessful follicles in the delivery category, then elevated FF-TRC was clearly associated with successful outcome. For individual women, the odds of infant delivery increased 17-fold as a function of average FF-TRC between 10,000 and 25,000 microIU/ml. For failed and delivery but not empty follicles, higher renin levels occurred in the smaller follicles, consistent with a burst of renin synthesis associated with the presence of an oocyte. The results suggest that FF-TRC relates to ovum viability with ovarian hyperstimulation and may have predictive use in IVF programmes.

Measurement of inactive renin in rat plasma: effect of nephrectomy and sialoadenectomy on the plasma concentration

In this paper we describe a routine method of measuring inactive renin in rat plasma. The activation was performed by trypsin, at optimal concentration and incubation conditions. The trypsin treatment formed an interfering and high-performance liquid chromatography-verified tetradecapeptide-like material, which was removed before the assay by a simple batchwise use of a cation-exchange resin. The concentration of activated inactive renin was measured by an antibody-trapping method after the addition of exogenous angiotensinogen. Angiotensinogen was added in order to compensate for the trypsin destruction of angiotensinogen and in order to measure the parameter of renin concentration. The inactive renin concentration in plasma of conscious male rats was 0.48 +/- 0.13 Goldblatt units (GU) per litre (n = 38). This corresponds to 66% (range 42-92%) of the total renin concentration. Physiological experiments in conscious rats were initiated, demonstrating that nephrectomy decreased the inactive renin concentration from 0.45 +/- 0.14 to 0.27 +/- 0.05 GU/l after 24 h (n = 21; P less than 0.01). Submandibular sialoadenectomy decreased the plasma inactive renin concentration from 0.45 +/- 0.11 to 0.34 +/- 0.06 GU/l (n = 12; P less than 0.05) after 7 days. Combined sialoadenectomy and nephrectomy decreased the plasma inactive renin concentration from 0.45 +/- 0.11 to 0.24 +/- 0.06 (n = 12; P less than 0.01).

Activation of the renin-angiotensin system during ritodrine treatment in preterm labor

Plasma renin activity, active renin concentrations, and total renin concentrations were measured serially in 15 women in preterm labor treated with ritodrine. All three parameters showed rapid increases during treatment that depended on ritodrine doses and paralleled changes in maternal pulse rate. The slope of the correlation between plasma renin activity and active renin concentrations suggested an increase in both active renin and renin substrate during ritodrine treatment. In contrast, levels of inactive renin remained unchanged for several hours during ritodrine infusion, showing only a late and much smaller response than that of either total or active renin concentrations. Thus ritodrine treatment results in further activation of an already activated renin-angiotensin system in pregnancy. This activation relates to an increase in both renin enzyme and its substrate. It may be responsible for the disturbance in water balance and the risk of pulmonary edema associated with beta-sympathomimetic drug treatment in preterm labor.

Identification and Quantification of Renin and Prorenin in the Bovine Eye

Angiotensin-II, the most important biologically active product of the renin-angiotensin system, has been reported to play a role in neovascularization, and prorenin has been found in the vitreous of human eyes, particularly in those affected by proliferative diabetic retinopathy, a disease characterized by neovascularization. The prorenin level in these eyes was, relative to that of plasma albumin, higher than in eyes without neovascularization. These findings suggested that an intraocular renin-angiotensin system exists, which might be involved in the development of retinal neovascularization in diabetes mellitus. In this study angiotensin-I-generating activity was measured in bovine aqueous humor and vitreous and in extracts of bovine retina, pigment epithelium-choroid, and anterior uveal tract before and after subjecting these extracts to procedures known to convert prorenin to renin. The measurements were made by incubation at 37 C with plasma from nephrectomized rats at pH ranging from 5.0-8.5. True renin in the ocular samples could be separated from nonrenin acid protease by alpha-casein-Sepharose affinity column chromatography at pH 3.5; true renin did not bind to the column, whereas acid protease did. True renin was further identified by its relatively high pH optimum (6.5-7.0) for angiotensin-I generation, its complete inhibition with specific renin antiserum, and its high affinity for specific renin inhibitors. More than 75% of angiotensin-I-generating activity of the ocular samples consisted of true renin. Approximately 90% or more of total renin (renin plus prorenin) in aqueous humor, vitreous, and ocular tissue could not be explained by trapped plasma. Total renin in aqueous humor and renin in vitreous were near the detection limit of the assay of angiotensin-I-generating activity. In vitreous prorenin comprised 99% of the total renin, in retina 81%, and in pigment epithelium-choroid and anterior uveal tract less than 50%. Prorenin in ocular fluids showed a concentration gradient, posterior vitreous greater than anterior vitreous greater than aqueous humor, suggesting that the main source of extracellular prorenin was in the posterior eye. These data support the contention of local renin and/or prorenin synthesis in the eye and are in accordance with the observations in other tissues that extrarenal synthesis of renin is often associated with the release of mainly, or exclusively, prorenin into extracellular fluid.

Release Mechanisms of Inactive Renin from Rat Renal Cortical Slices: Role of the Submandibular Gland

In our previous studies, we showed an in vivo stimulating effect of the extract of the rat submandibular gland on plasma inactive renin release. In this study, we evaluated the effects of the rat submandibular gland extract and of some plasma active renin stimulants on inactive renin release from rat renal cortical slices. Adult male Wistar rats (250-350g) were kept on a regular diet (Na 260mg/100g) and nephrectomized under pentobarbital anesthesia (50mg/kg, i.p.). Five thin renal cortical slices were obtained from each kidney by using a razor blade. These renal cortical slices were incubated in Earle's buffer (pH7.4, Difco) at 37 degrees C for 30 min (preincubation), then transferred into 10ml fresh Earle's buffer with or without some agents and incubated at 37 degrees C for 1 hour (experimental incubation). For each experiment, 6 groups of 5 renal cortical slices were employed. The agents used in this study were as follows: isoproterenol (10(-5)M), furosemide (50 micrograms/ml), prostaglandin E1 (10(-5)M), prostaglandin I2 (10(-5)M) and the rat submandibular gland extract (100 microliters) which was obtained after homogenation with 10 x (w/v) 0.01M pyrophosphate buffer (pH6.5) including 0.1M NaCl. One ml of samples of this Earle's buffer were withdrawn every 20 min. Active renin in the samples was assayed by the commercial RIA-kit (Dainabot), and total renin was assayed after trypsin (Worthington) treatment (30 micrograms/300 microliters sample) at 4 degrees C for 10 min. Inactive renin was determined as the difference between total renin and active renin. Active and inactive renins increased linearly in the buffer without any agents (control) during the observation period (60 min). Isoproterenol (10(-5)M) stimulated the release of active renin significantly (p less than 0.01 vs. control) but did not affect the release of inactive renin. Furosemide (50 micrograms/ml) stimulated the release of active and inactive renins significantly at 20 and 40 min (p less than 0.05 vs. control) but did not affect the release of either renin at 60 min. Both prostaglandins E1 and I2 (10(-5)M) stimulated the release of active renin significantly (p less than 0.01 vs. control) but inhibited, on the other hand, the release of inactive renin significantly (p less than 0.01 vs. control). The rat submandibular gland extract (100 microliters) did not affect the release of active renin but stimulated the release of inactive renin significantly (p less than 0.05 vs. control).(ABSTRACT TRUNCATED AT 400 WORDS)

Role of the Submandibular Glands in In Vivo Mechanisms of Plasma Inactive Renin Release in the Rat

In our present studies, we evaluated the role of the submandibular glands (SMG) on plasma inactive renin (PIR) releasing mechanisms in rats using some agents which are known to stimulate plasma active renin (PAR) release. The results were analyzed between sialoadenectomized (SX) and sham-operated (control: C) rats. Twenty-four h after the operation, PAR releasing agents, furosemide (FRO) 2.5 mg/rat/h with prior iv bolus 5 mg, captopril (CAP) 5 mg/rat/h with prior iv bolus 10 mg, 1-Sar-8-Ile-angiotensin II (Ang II A) 300 ng/kg/min, prostaglandin E1 (PGE1) 100 ng/kg/min, and prostaglandin I2 (PGI2) 100 ng/kg/min, were infused through femoral venous cannulae. Blood samples were taken through femoral arterial cannulae into test tubes containing 2 mg EDTA-2Na. PAR was assayed by RIA, and total renin was obtained after tryptic activation. According to the responses of PIR, the agents used were categorized into three patterns: FRO increased PIR, both PGs lowered PIR, and, CAP and Ang II A had no effect on PIR release. The PIR release mechanisms by FRO were further investigated by 20 mg FRO ip injection in totally nephrectomized rats. PIR increased even in nephrectomized rats, but the increase was totally canceled by the following SX. In conclusion, FRO alone among some agents studied is able to stimulate PIR release only under the existence of SMG.

Plasmaspiegel des atrialen natriuretischen Peptids (ANP) nach oraler Glycerolbelastung

Atrial natriuretic peptide (ANP) is a cardiac hormone known to mediate increased capillary permeability, vasodilation, and natriuresis. In 1988 the authors' experimental results indicated the presence of ANP receptors in the inner ear. From this they hypothesized that ANP might be involved in the regulation of inner ear fluids and therefore investigated the effects of orally administered glycerol on ANP and cGMP plasma levels. As regards the initial values, there was no apparent significant difference between the 14 subjects with Ménière's disease and the 34 subjects without. During the first hour after glycerol administration there was a significant hormonal effect: ANP, cGMP (second messenger), and serum osmolality increased, while total serum protein and plasma renin decreased. In addition to this, the hearing ability of ten subjects was positively affected. After the first hour the hormonal levels reapproached their original homeostatic states. But the positive effects on hearing ability continued to increase for another hour before decreasing again. The authors believe that this delayed effect is caused by the blood-perilymph barrier. Further research is required to establish whether glycerol affects hearing improvement directly or by mobilizing ANP.