Prorenin Concentrations Research Articles

Zonal distribution and regulation of adrenal renin in a transgenic model of hypertension in the rat

The hypertensive transgenic rat [TGR (mRen-2)27] is a genetic model of hypertension in which transfection of the Ren-2 mouse renin gene into rats results in severe hypertension. These transgenic rats express a high level of renin in the adrenal gland, and the hypertension is ameliorated by treatment with angiotensin-converting enzyme inhibitors. In this study we investigated the distribution of adrenal renin in the TGR rat and examined the regulation of adrenal renin in a monolayer culture of adrenal cells. High concentrations of active renin and prorenin were found in the adrenal capsular (glomerulosa) and decapsular (fasciculata-medullary) portions of the TGR adrenal. This is in contrast with the Sprague-Dawley (S-D) rat, in which adrenal renin is found mostly in the active form and located primarily in the glomerulosa cells. The zonal distribution of aldosterone was also different in the TGR, with substantial amounts of aldosterone in the zona fasciculata as well as in the glomerulosa, while in the S-D rat, aldosterone is limited to the zona glomerulosa. In the primary monolayer culture of glomerulosa cells, TGR cells had significantly higher levels of active renin and prorenin and showed an increased response to ACTH and high potassium in the medium. Renin activity in the medium was predominantly in the form of prorenin and significantly higher than that in the S-D rat. Cultured fasciculata cells from TGR also produce renin that is stimulated by ACTH, but not by a high potassium concentration. Renin activity in the adrenal homogenate, medium, and plasma from TGR rats was completely inhibited by the renin inhibitor (CP 71362; 1 microM), but only slightly inhibited (12.3 +/- 3%) by a monoclonal antibody that inhibits renin activity from S-D rat tissues by 79.2 +/- 2.5%, suggesting that renin in the plasma and adrenal glands from TGR appears to derive primarily from mouse renin. In conclusion, the TGR (mRen-2)27 rats have higher than normal levels of adrenal renin, and the cultured cells show an exaggerated renin response to ACTH and potassium. The distribution of the renin enzyme in the adrenal zones of the TGR is similar to the distribution of mouse adrenal renin.

Prorenin is present in plasma from nephrectomized rats

The aim was to demonstrate whether prorenin is present in plasma from 24-h nephrectomized rats. Its existence and concentration is currently under debate. Determination of the 50% inhibition concentration (IC50) values for inhibition of plasma renin in intact and 24-h nephrectomized rats. The potent and specific rat renin inhibitor CH-732 was used. Our previously published method for the determination of rat prorenin was used. It is characterized by removal of an interfering trypsin-formed angiotensin I immunoreactive material before the renin incubation step. The trypsin-activated prorenin-like activity of 24-h nephrectomized plasma was due only to a minor degree to real prorenin as judged by CH-732 inhibition. The major part of the prorenin-like activity was due to a hitherto unknown sulphydryl enzyme, which could be blocked by N-ethylmaleimide. In normal plasma all prorenin was real prorenin. The plasma concentration of real prorenin in 24-h nephrectomized rats was approximately 10% of that in intact rats. Prorenin is definitely present in nephrectomized plasma, but in low concentrations. The data support the concept that the major part of plasma prorenin in intact rats originates from the kidneys. The previously published values for prorenin in intact rats were correct, whereas those in 24-h nephrectomized rats were too high. If N-ethylmaleimide is added to our previously published method for rat prorenin, it overcomes the three known problems with prorenin determination in rat plasma: trypsin generation of angiotensin I immunoreactive material; trypsin destruction of angiotensinogen; and interference in trypsin-activated nephrectomized plasma of a sulphydryl enzyme, which generates an angiotensin-I-like material.

Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy

Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy

Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy.

Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases 10-fold throughout pregnancy to 10-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient underwent surgery at 5 5/7 weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (Vmax) (16 and 3 sacs, respectively) averaged 6,100 +/- 1,700 (SD) and 1,930 +/- 760 ng/mL.h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin Vmax was 10-fold higher, averaging 62,500 +/- 40,000 ng/mL.h (17,000 ng/L.s). The concentration was 140,000 ng/mL.h (39,000 ng/L.s) in the 5 5/7 week tubal pregnancy. In sharp contrast, at 10-12 weeks gestation (n = 3) prorenin Vmax was only 260 +/- 114 ng/mL.h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 +/- 110,900 IU/L) and lowest at 10-12 weeks (1210 +/- 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 micrograms protein/mL) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation.

A direct immunoradiometric assay for human plasma prorenin: concentrations in cycling women and in women taking oral contraceptives.

Two synthetic penta deca peptides corresponding to the N-terminal portion (amino acid sequence 1-15) and the C-terminal portion (sequence 32-46) of the pro moiety of the human prorenin (PR) molecule were coupled to BSA and used as antigens to generate antibodies against PR. In a RIA system using the 125I-labeled peptide as tracer, it could be shown that antibodies against peptide 32-46 bound the peptide and the native PR in the follicular fluid (FF) to a similar degree, whereas antibodies generated against peptide 1-15 did not specifically recognize native PR. The specificity of the PR-(32-46) antibodies for PR was demonstrated by comparative measurements of PR by RIA and by an indirect procedure (involving trypsin treatment of PR) in different individual FF samples, plasma samples, and fractions of FF obtained by gel filtration or immunoaffinity chromatography. Normal plasma PR levels could not be measured by RIA, since they were below the detection limit of the assay (0.5 micrograms PR/L approximately 10 pmol/L). For measurement of the low PR levels in plasma, a sensitive direct immunoradiometric assay with a detection limit of 0.1 fmol PR/tube was developed. It was based on the combined action of a commercially available solid phase renin antibody and the affinity-purified and 125I-labeled PR-(32-46) antibody. The measurement of 35 individual plasma samples with different PR concentrations showed an excellent correlation (r = 0.99) between the new direct and the conventional indirect assays. The direct assay of PR concentrations in plasma of healthy women during the length of a menstrual cycle resulted in a biphasic pattern of PR concentrations, with peak levels (approximately 3-fold increase) at the time of the LH surge. The intake of monophasic and triphasic contraceptives caused a suppression of normal PR concentrations (96.9 +/- 34 ng/L; early follicular phase; n = 12) by 39% and 25%, respectively, which was also observed in the pill-free phase of the artificial cycle.

Effects of prorenin on blood pressure and plasma renin concentrations in stroke-prone spontaneously hypertensive rats.

To examine the possible activation of prorenin in the circulation, recombinant rat prorenin was intravenously given to pentobarbital-anesthetized rats. Bolus injection of prorenin at the dose of 100 micrograms angiotensin I (ANG I).h-1.kg-1 into Wistar rats, leading to a 15-fold increase in plasma prorenin concentrations (from 27 +/- 6 to 393 +/- 75 ng ANG I.h-1.ml-1) at 5 min after the injection, did not affect blood pressure, heart rate, and plasma active renin concentrations throughout experiments. On the other hand, the administration of active renin at the dose of 1, 3, and 10 micrograms ANG I.h-1.kg-1 increased mean blood pressure of Wistar rats by 8 +/- 2, 15 +/- 2, and 27 +/- 4 mmHg, respectively. Similar results were obtained in Wistar rats at 18 h after bilateral nephrectomy. These results confirmed no activation of prorenin in the circulation of normotensive rats. The activation of prorenin was also examined on both stroke-prone spontaneously hypertensive rats (SHRSP) and 18 h-nephrectomized SHRSP. There was no rise in blood pressure or plasma active renin concentrations in both groups of SHRSP after injection of prorenin. Thus the elevated plasma active renin in SHRSP [Shibota, M., A. Nagaoka, A. Shino, and T. Fujita. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H409-H416, 1979] seems to be caused by the enhanced release of active renin from the kidney rather than the activation of circulating prorenin.

Activation and function of prorenin: different viewpoints

This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and its presence in extrarenal, as well as renal, tissues. Intriguing changes in plasma prorenin have been reported after treatment with antihypertensive and other drugs, following various physiological stimuli, and in pathophysiological states such as Wilms' tumor, Bartter's syndrome, and diabetic nephropathy. Lately, very high prorenin concentrations have been found in human and animal ocular fluid, ovarian follicular fluid, and in association with angiogenesis and microangiopathy. High circulating prorenin concentrations and fulminant hypertension have been reported in rats harbouring the mouse Ren-2 gene. However, what prorenin does in all these extrarenal fluids, tissues, and conditions is not well understood. Among the reasons for this lack of understanding are the difficulties in measuring prorenin and in establishing good animal models. We have not answered the critical question as to whether prorenin itself is bioactive like a hormone, and if so, what its action(s) might be. Nor have we established the main alternative, i.e., whether the function of prorenin is indirect, through renin--angiotensin, be it in the circulation or in the extrarenal tissues. This Symposium provides only partial methodological advances and answers, but we hope it will stimulate the breakthrough work needed to supply more complete answers.

Perfusion-microcarrier cultivation of rCHO-cells in serum-free medium for production of human renin

A recombinant CHO cell line producing human prorenin was cultivated on microcarriers in serum-free medium. Best growth was obtained when the cells were cultivated on a collagen coated microcarrier (Cytodex 3) using a serum-free medium (SF-02) supplemented with fibronectin. It was possible to reduce the necessary concentration of fibronectin in the feed medium from 10 μg/cm3 to 2 μg/cm3 during perfusion cultures in a spinner reactor equipped with an UF-membrane. Also in this system, the prorenin concentration increased up to 8 times higher compared to that in a conventional repeated-batch culture. The cells grew in multilayers on the microcarriers during the perfusion culture. The specific prorenin productivity was not significantly affected by the cell growth rate, and the secretion of prorenin continued even after the cells had ceased to grow.

EFFECT OF GONADOTROPINS AND PREGNANCY ON PRORENIN AND RENIN IN THE RAT

1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two-fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two-fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG. 2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one-third of that in normal female rats. In contrast active renin in the uterus was increased about two-fold in the first trimester, whereas prorenin did not change consistently. 3. Our results confirm that gonadotropins and pregnancy affect the renin-angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction in the rat.

Tissue renin and prorenin increase in female cats during the reproductive cycle without commensurate changes in plasma, amniotic or ovarian follicular fluid.

The renin gene is expressed, primarily as prorenin, in the ovary, uterus and placenta. High concentrations of prorenin are present in human ovarian follicular and amniotic fluids and ovarian secretion causes increases in plasma prorenin at mid-menstrual cycle and during pregnancy. Plasma prorenin is low but detectable in nephrectomized human subjects. Comparative studies in female cats revealed several differences. Cat plasma prorenin became undetectable after bilateral nephrectomy. Neither plasma prorenin nor renin increased during pregnancy. Renin and prorenin were undetectable in ovarian follicular, amniotic and allantoic fluids. Human chorionic gonadotropin-induced ovulation caused only small increases in plasma prorenin. In contrast, renin and prorenin were clearly present in extracts of reproductive tissues. Ovarian total renin was lowest during anestrus (169 +/- 27 ng/g per h) and estrus (258 +/- 58 ng/g per h) and increased with ovulation (385 +/- 31 ng/g per h). Higher ovarian levels were found during pseudopregnancy (1370-2030 ng/g per h) and early pregnancy (1312-2700 ng/g per h) and in the placental chorion disc of early pregnancy (1755-1184 ng/g per h). In the uterus, the level was 98-183 ng/g per h during gestation. These results demonstrate that, in marked contrast to humans, only the cat kidney secretes prorenin into body fluids. Nonetheless, total renin increases in cat ovaries during follicle maturation, ovulation, pregnancy and pseudopregnancy, in the uterus during gestation and in the placental chorion disc. These results are consistent with an autocrine or paracrine role for the tissue renin system in cat reproductive tissues.

Increased plasma prorenin but not renin after bilateral ureteral ligation in dogs

Plasma prorenin is normally higher than renin and usually changes in response to the same stimuli. In dogs, plasma prorenin and renin disappear after bilateral nephrectomy, indicating that both are of renal origin. It has been proposed that prorenin may mediate tissue renin systems via its reversible intrinsic renin-like activity. The renin-angiotensin system has been implicated in the changes in renal function that occur with bilateral ureteral obstruction, but plasma prorenin has not been investigated. We therefore studied the effect of 48-hour bilateral obstruction on plasma prorenin in two groups of dogs: one was volume expanded (N = 5), while the other group (N = 6) was euvolemic. Plasma prorenin concentration increased fourfold in both groups, angiotensinogen increased twofold, while plasma renin activity was unchanged. Following release of obstruction, plasma renin fell slightly while prorenin and angiotensinogen remained elevated. There was a positive relationship between plasma prorenin and renin before (r = 0.63, P less than 0.05) and after (r = 0.76, P less than 0.01) obstruction. Post-obstruction, ERPF and GFR were subnormal but filtration fraction was maintained; the higher the ERPF and GFR the higher the plasma prorenin post-obstruction (r = 0.83, P less than 0.01 and r = 0.77, P less respectively; N = 11). These results show that impairment of renal function during bilateral obstruction is associated with an increase in plasma prorenin but not renin. Nonetheless, there is a positive relationship between plasma prorenin and renin both pre- and post-obstruction. Thus, preferential impairment of clearance of prorenin relative to renin may occur during bilateral obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological evidence that kidney is primary source of circulating inactive prorenin in rats

To determine whether or not rat plasma inactive renin is prorenin, specific antibodies were raised against two 15-amino acid peptides, Pro-NH2 and Pro-COOH, which contained the NH2-terminal and COOH-terminal sequences, respectively, of the prosegment of rat prorenin. Inactive renin was measured after trypsin treatment. Immunoaffinity chromatography of normal rat plasma on anti-Pro-NH2 and anti-Pro-COOH immunoglobulin G (IgG)-Sepharose showed that about one-half the amount of inactive renin was prorenin, whereas the rest was neither prorenin nor renin. Thus trypsin treatment of the unfractionated plasma does not provide measurement of the concentration of prorenin. However, fractionation of plasma by high-performance liquid chromatography on G3,000SW columns followed by trypsin treatment led to the measurement of prorenin. Prorenin and active renin concentrations in the normal plasma of conscious rats were 44.3 +/- 5.8 and 13.3 +/- 1.4 (SE) ng ANG I.h-1.ml-1, respectively (n = 10). On the other hand, plasma inactive renin from rats at 24 h after bilateral nephrectomy bound to neither anti-Pro-NH2 nor anti-Pro-COOH IgG immunoaffinity columns, and the enzymatic activity after trypsin treatment was not inhibited by anti-mature renin IgG. These results demonstrate that inactive renin from nephrectomized rats was not prorenin. Thus the kidney is the primary source of circulating prorenin in rats.

Measurement of renin and prorenin in cattle, hog and horse

1. 1. Species specific problems complicating the measurement of prorenin and renin concentrations were studied in bovine, hog and horse plasma. 2. 2. In contrast to horse renin, bovine and hog renin reacted with rat angiotensinogen, allowing measurement of the plasma renin concentration in cattle and hog with rat angiotensinogen as exogenous substrate. 3. 3. Trypsin treatment of plasma in order to activate prorenin generated an interfering angiotensin I immunoreactive material in all three species, most extensively in horse plasma. 4. 4. This material could be removed in bovine and hog plasma by a cation-exchange resin, allowing an assay of the plasma prorenin concentration to be constructed in these species. 5. 5. Another strategy has to be followed in order to measure prorenin and renin concentrations in horse plasma.

A Case of Renin Producing Leiomyosarcoma Originating in the Lung.

A 54-year-old woman was referred to our hospital for the treatment of a tumor of the right chest wall. Clinical examination revealed hypertension, hypokalemia, metabolic alkalosis, hyperaldosteronism and hyperreninemia. Computed tomography and an abdominal echogram indicated a tumor in the right phrenic area and two tumors in the retroperitoneum near the pancreas head. After the surgical resection of these tumors, the primary reninism was diminished. The pathological diagnosis of these tumors was leiomyosarcoma. Plasma active and inactive (trypsin-activated) renin activities (PRA) were 85.7 and 38.9 ng angiotensin I/ml/h, respectively. These PRA did not respond to either postural stimulation or suppression by the volume expansion. Active and inactive renin activities in a right phrenic area tumor were 208 and 32 ng angiotensin I/mg protein /h, respectively. Those of an abdominal tumor were 196 and 30 ng angiotensin I/mg protein/h, respectively. Renin mRNA identical in molecular size to that of the human kidney was identified by northern blot analysis. This is the first case report of renin producing leiomyosarcoma derived from the lung, which is characterized by relatively lower plasma prorenin concentrations.

Raised plasma renin and prorenin in rheumatoid vasculitis.

The value of plasma renin and its inactive precursor, prorenin, were examined as a marker for vasculitis in rheumatoid arthritis (RA). Plasma renin and prorenin rise when the renin-angiotensin system is activated; an isolated increase of prorenin may be a marker for microvascular complications in diabetes mellitus. Renin concentrations in plasma obtained from 34 patients with RA (seven with vasculitis, 27 controls) were measured under standard conditions, before and five days after stopping non-steroidal anti-inflammatory drugs; creatinine clearance was also measured. At first the median renin concentration in the patients with vasculitis was 19 (range 12-63) mU/l (normal less than 61 mU/l) and in the controls 9 (3-43) mU/l. The median prorenin concentration in patients with vasculitis was 233 (144-428) mU/l (normal less than 358 mU/l) and in the controls 144 (25-364) mU/l. Renin and prorenin concentrations increased significantly in both groups after withdrawal of nonsteroidal anti-inflammatory drugs. The creatinine clearance was similar in both groups and did not correlate with renin concentrations. In conclusion, it was found that, unlike patients with diabetes mellitus, patients with RA with vasculitis had slightly raised concentrations of both renin and prorenin. These findings signal activation of the renin-angiotensin system and might indicate early cardiac or renal involvement by vasculitis.

Chemical characterization of angiotensin I in porcine follicular fluid

In the search for novel neuropeptides in porcine follicular fluid (pff) using smooth muscle contractile activity as a response parameter, a substance with a marked activity was isolated in a pure form. By amino acid analysis and sequential study, this substance has been chemically revealed to be angiotensin I. A much smaller amount of additional activity was isolated and found to be angiotensin II, as determined by radioimmunoassay. Radioimmunoassays for angiotensin I and II confirmed that the amount of angiotensin I determined was much greater than that of angiotensin II. A comparative study of the extractions, however, indicated a large amount of angiotensin I had been generated from angiotensinogen by endogenous renin in the follicular fluid which could be activated during extraction and ultrafiltration at a low pH. These findings are consistent with the previous reports that described a high concentration of prorenin in the follicular fluid, acid activation of prorenin to renin and the subsequent generation of angiotensin I from endogenous angiotensinogen.

Immunoreactive renin variations during fertile and infertile hyperstimulated cycles with in-vitro fertilization and embryo transfer or gamete intra-fallopian transfer.

The concentrations of prorenin (PR) and active renin (AR) were determined sequentially during ovarian hyperstimulated cycles for in-vitro fertilization-embryo transfer or gamete intra-Fallopian transfer. AR and PR increased during the early luteal phase and PR was highly correlated with the progesterone concentration. In fertile cycles, AR increased more rapidly after HCG injection and AR and PR levels were significantly higher during the late luteal phase. These results confirm the role of the renin angiotensin system in ovarian physiology.

Prorenin and renin as separate mediators of tissue and circulating systems.

The renin gene is expressed in extrarenal tissues. High concentrations of renin occur in female reproductive organs: the adrenals of rats and mice have intermediate levels. The testis also synthesizes renin, as does the anterior pituitary. In contrast, very low levels of renin (ie, below plasma levels) are found in the heart and extrarenal vascular tissues. The predominant form of renin in the human ovary, placenta, and uterus is prorenin and the human ovary, testis, and adrenals have been shown to secrete prorenin into the circulation. The kidney is the only organ that secretes active renin and it is also the major source of plasma prorenin. We have used the ovary as a model to study extrarenal renin. Ovarian prorenin secretion changes dynamically during the menstrual cycle and during gestation. Secretion occurs during the LH surge and when hCG is present in the blood during pregnancy. Plasma active renin does not change concurrently and only low levels of active renin are found in association with very high concentrations of prorenin in ovarian follicular fluid after gonadotropin stimulation. To explain the preponderance of prorenin, and the virtual absence of renin in the ovary we hypothesize that prorenin need not be converted to active renin to have effect. In vitro, when prorenin is acidified to pH 3.3 or cooled to 0 degrees C, it develops intrinsic catalytic activity without cleavage of the prosegment.(ABSTRACT TRUNCATED AT 250 WORDS)

The ovarian prorenin-angiotensin system. Lessons from IVF.

Recent evidence suggests that prorenin and other active components of the renin-angiotensin system may be linked to ovarian physiology. Prorenin, the inactive form of the enzymatically active renin, is present in the fluid of mature human ovarian follicles in concentrations more than 10 times higher than that found in the plasma of women undergoing ovarian stimulation. Only 1% of the renin in follicular fluid is in active form. Concentrations of prorenin in fluid of immature follicles are lower than levels detected in concomitantly aspirated mature follicles. Study of prorenin levels disclosed a positive correlation to testosterone and E2 in fluids of mature follicles. Plasma prorenin increases about twofold at midcycle at the time of the LH surge; the peak of prorenin is sustained for about 40 hours. In patients undergoing ovarian stimulation for IVF, hCG administration results in much higher plasma prorenin levels and the height of prorenin response is directly related to the number of mature follicles. It peaked 4 to 6 days after hCG injection and then fell, close to baseline, by about 12 days after hCG administration. Examination of the time course of hormonal changes in response to hCG revealed a temporal relationship between prorenin and both plasma E2 and progesterone. In women who conceived, prorenin began to rise again on days 8 to 12 after embryo transfer when endogenous hCG was detected in the blood. No such changes in prorenin occurred in women with ovarian failure who conceived after transfer of a donor egg. These findings indicate that prorenin is produced by the mature follicle and the corpus luteum in response to LH/hCG. Since angiotensin II affects intracellular calcium and phospholipase activity, there are many potential roles for prorenin via angiotensin II action. Putative actions of the ovarian renin system may include control of oocyte maturation, ovulation, ovarian blood flow, and ovarian steroid biosynthesis. Future work to elucidate the function of this new renin system may have relevance to many basic and clinical aspects of human reproduction.

Plasma prorenin and renin in childhood and adolescence.

We studied 108 subjects (age range, 4 to 76 years) to determine the effect of age on prorenin (inactive renin), active renin, and plasma renin activity in normal children, adolescents, and adults. Children and adolescents had lower prorenin concentrations and higher plasma renin activity and active renin concentrations than did adults. Prorenin concentrations were positively correlated with age over the range of 4 to 76 years, while plasma renin activity and active renin concentration were negatively correlated with age. Plasma prorenin and active renin concentrations from umbilical cord blood samples obtained from 11 newborns and arterial samples obtained from five infants were higher than those in samples obtained from children or adults.