Plasma Renin Substrate Concentration Research Articles

Effect of an oral contraceptive containing drospirenone on the renin-angiotensin-aldosterone system in healthy female volunteers

Drospirenone is a new synthetic progestogen with both progestational, antimineralocorticoid and antiandrogenic properties. In combination with ethinylestradiol, it is being developed as an oral contraceptive which will contain 30 μg ethinylestradiol and 3 mg drospirenone (Yasmin®, Schering AG, Germany). The effects of drospirenone alone, and in combination with ethinylestradiol, upon the renin–angiotensin–aldosterone system (RAAS) have been evaluated in healthy female volunteers. RAAS activity was assessed by measurement of plasma renin substrate (PRS) concentration (otherwise known as angiotensinogen), plasma renin activity (PRA), and plasma aldosterone (P-Aldo) concentration. An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5–3.0 mg/day for one cycle. The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA. When ethinylestradiol (30 μg) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles, an increase in PRS was observed with both preparations, which was indicative of estrogenic stimulation, and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone. Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3. The effect of the preparation containing 30 μg ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 μg ethinylestradiol but combined with 150 μg desogestrel (Marvelon®). Over a period of 13 cycles, increases in PRS were seen with both treatments, the effect being slightly more pronounced with 30 μg ethinylestradiol/150 μg desogestrel. A markedly greater increase in PRA was seen following treatment with 30 μg ethinylestradiol/3 mg drospirenone, and, in cycle 3, this difference was statistically significant. In contrast, P-Aldo was increased markedly with 30 μg ethinylestradiol/3 mg drospirenone in all measured cycles, whereas, in the 30 μg ethinylestradiol/150 μg desogestrel group, changes were minimal. The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone. PRS increases under all combinations are an expression of estrogenic stimulation. Measurement of body weight and blood pressure in the studies with combined ethinyl-estradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight, while blood pressure remained largely unchanged. Overall, the results indicate that 30 μg ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect.

Atrial Natriuretic Peptide in the Preterm Newborn

Atrial natriuretic peptide (ANP), plasma renin and renin substrate concentrations (PRC and PRS) were measured in 31 preterm infants with idiopathic respiratory distress syndrome. Infants were studied at a mean of 1.4 days; 17 infants were also studied 2 days later. A 6-hour urine collection was made from 13 male infants on the first day of sampling to assess renal function. Both ANP and PRC were elevated and showed wide ranges of values (geometric means of 620 pg/ml and 18.4 ng/ml/h). Plasma ANP was significantly correlated with pH, PaCO2 and base excess. No correlations with parameters of cardiovascular or renal function were found. Plasma ANP rose in 13 of the 17 paired samples. We suggest that the very high ANP concentrations in these babies are a consequence of the pulmonary haemodynamic disturbances which accompany respiratory distress in the newborn.

Longitudinal study of platelet angiotensin II binding in human pregnancy.

1. Platelet angiotensin II binding, circulating angiotensin II levels, plasma renin substrate and plasma renin concentration were measured in a longitudinal study of 30 women during pregnancy and the puerperium. 2. There was a significant fall in platelet angiotensin II binding from 11 weeks gestation to 18 weeks gestation (P less than 0.01). There were no further significant changes in platelet angiotensin II binding until after delivery, a significant rise in platelet angiotensin II binding being found at 6 weeks post partum as compared with at 36 weeks gestation (P less than 0.01). There was no further significant change from 6 to 12 weeks post partum, and platelet angiotensin II binding at 6 and 12 weeks post partum in the pregnant cohort approximated to that in nonpregnant women. These changes parallel those known to occur in pressor responsiveness to angiotensin II in pregnancy. 3. Plasma angiotensin II concentration, plasma renin substrate and plasma renin concentration were all significantly higher during pregnancy than in the puerperium (P less than 0.001). There were no significant changes during pregnancy in plasma angiotensin II concentration or plasma renin concentration, although plasma renin substrate rose throughout. 4. Significant inverse correlations between platelet angiotensin II binding and plasma angiotensin II concentration (P less than 0.01), plasma renin substrate (P less than 0.01) and plasma renin concentration (P less than 0 greater than 001) were found during pregnancy. These data suggest that down-regulation of platelet angiotensin II binding by the components of the renin-angiotensin system pertains in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Low angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements

purpose: To compare the determination of plasma renin activity (PRA) and the direct measurement of active renin by immunoradiometric assay (IRMA) as methods of assessing the renin system in patients with congestive heart failure. patients and methods: The status of the renin-angiotensin system in congestive heart failure was assessed by measuring the plasma renin substrate concentration, PRA, and plasma concentration of active renin in 37 patients with mild to severe congestive heart failure. Natremia and plasma levels of atrial natriuretic factor (ANF) were determined as biologic indexes of the severity of heart failure, and concentrations of prealbumin and retinol-binding protein were used as indexes of liver dysfunction. results: The PRA and the concentrations of active renin and ANF were markedly higher in patients with New York Heart Association class IV heart failure than in patients with class II to III heart failure, while natremia and the concentrations of renin substrate, prealbumin, and retinol-binding protein were markedly lower in the class IV patients than in the class II to III patients. Plasma renin substrate concentration was negatively correlated with active renin concentration (n = 37, r = −0.45, p = 0.005), and positively related to natremia (r = 0.56, p <0.0005), prealbumin (r = 0.54, p <0.001), and retinolbinding protein (r = 0.60, p <0.0001). conclusions: Low levels of plasma renin substrate can be considered as an indirect index of the severity of heart failure that reflects both the high level of circulating active renin and the decrease in hepatic protein output. In patients with class IV heart failure, low levels of renin substrate led to a marked underestimation of active renin concentration from measurements of PRA. In contrast, direct IRMA of active renin measures the true plasma active renin concentration, independent of plasma renin substrate, and closely reflects renin secretion.

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)

Plasma renin and renin substrate concentrations in the very premature human baby : F.B. Pipkin and T.J. Stephenson a, Department of Obstetrics and Gynaecology and aDepartment of Child Health, Queen's Medical Centre, Nottingham, U.K.

Three discriminant functions were used to determine which were the most effective in discriminating between death and survival of an infant, and to assess the importance of each independent variable in the analyses. Model A contained 28 variables which had been found significant or borderline in previous regression analyses upon birth weight, gestation, or crown-heel length. Model B consisted only of birth weight, gestation, and crown-heel length, while Model C contained the 25 variables of Model A not included in Model B.Model A was judged to be the most effective in discrimination. Model B, with only three variables, was almost as powerful. Model C, with 25 variables, was the least effective by far.The three variables of Model B were further analyzed to determine which of these three indices of prematurity, and which combinations of them were most important in discriminating between death and survival. Birth weight was the most powerful, gestation was next, and crown-heel length the least important. Considering the variables in pairs, birth weight and gestation was the most effective pair, followed by birth weight and crown-heel length. Gestation and crown-heel length was the least effective. Birth weight alone was a better discriminator than gestation and length combined. Furthermore, the addition of a third index to any given pair significantly increased the discriminating power of the function.Individual variables, other than the three discussed above, found significant in discrimination included race, sex, prepregnancy weight of the mother, obstetric complications, placenta and cord conditions, and congenital malformations.

No Effect of Short Term Angiotensin II Infusion on Plasma Renin Substrate Levels in Man*

We studied the effect of angiotensin II (A-II) infusion (4 ng/kg BW.min) on plasma renin substrate (RS) levels and PRA in five normal men during normal, diuretic-stimulated, and enalapril-interrupted function of the renin-angiotensin system. A-II infusion increased (15-25%) both systolic and diastolic blood pressure in the normal state and during angiotensin-converting enzyme inhibition, whereas the increase during diuretic-stimulated renin-angiotensin system function was less. The plasma RS concentration was measured by both direct and indirect RIA. The mean basal plasma RS levels, measured with direct assay, were 1516 +/- 150 (SE) in the normal state, 1566 +/- 150 after diuretic administration, and 1650 +/- 133 nmol/L after enalapril administration. The corresponding mean basal plasma RS levels measured with the indirect assay were 1073 +/- 100, 1031 +/- 57, and 902 +/- 78 nmol/L, respectively. Plasma RS levels did not change during or after the A-II infusions, whereas PRA decreased significantly in all experimental conditions. The results suggest that A-II exerts no direct stimulatory effect on hepatic release of RS. Thus, A-II appears not to be important in the short term regulation of plasma RS levels.

ACUTE HORMONAL AND RENAL EFFECTS OF ORAL DILEVALOL IN NORMAL MEN

1. Acute hormonal and renal effects of dilevalol (200 mg), a non-selective beta-blocking drug with vasodilator properties, were compared with placebo in six normal men on constant sodium intake. 2. Control and treatment blood pressures were lower with dilevalol than placebo, although the pattern of blood pressure fall was similar in both. 3. Plasma active renin and aldosterone concentrations were lower on dilevalol than placebo after 4 h of recumbency (P less than 0.05). 4. Total plasma renin, renin substrate, cortisol and atrial natriuretic peptide concentrations were similar on dilevalol and placebo. 5. There were no differences in glomerular filtration rate and no deleterious biochemical or haematological changes on dilevalol or placebo.

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.

Changing basal and stimulated activity of the renin-angiotensin system during the second half of gestation in the anaesthetized piglet.

Concentrations of components of the renin-angiotensin system were studied in eighty anaesthetized pig fetuses aged between 57 and 112 d of gestation (term = 114 +/- 1 d). Plasma renin concentration rose from a mean value of 3.2 +/- 0.4 ng X ml-1 X h-1 (mean +/- S.E.M.) at 57 d to 17.5 +/- 2.7 ng X ml-1 X h-1 at 93 d of gestation and thereafter declined to 5.0 +/- 1.6 ng X ml-1 X h-1 just prior to term. There was no distinct pattern of change in plasma renin substrate concentrations during gestation; the concentration near term (0.33 +/- 0.10 micrograms X ml-1) was not different from that at 57 d (0.50 +/- 0.18 micrograms X ml-1) or that at 93 d (0.31 +/- 0.08 micrograms X ml-1) of gestation. Plasma angiotensin II concentrations increased from 33 (log10 (mean +/- S.E.M.) = 1.554 +/- 0.050) pg X ml-1 at 60 d to 232 (2.365 +/- 0.225) pg X ml-1 at 105 d of gestation, after which it decreased to 50 (1.699 +/- 0.100) pg X ml-1 in 20-d-old neonatal piglets. Haemorrhage of 10-20% estimated blood volume produced no consistent changes in plasma renin substrate concentrations, and inconsistent changes in renin and angiotensin II concentrations at 85-90 d of gestation, but a consistent increase in both renin and angiotensin II concentrations thereafter. These results indicate that the components of the renin-angiotensin system are present in the circulation of the pig fetus, and that their responses to stimuli develop during the second half of gestation.

Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma.

To investigate the effect of aging on the renin-angiotensin-aldosterone system, plasma renin substrate concentrations (PRSC); plasma total, active, and inactive renin concentrations (TRC, ARC, and IRC); PRA; and plasma aldosterone concentrations (PAC) were measured simultaneously in 60 normal subjects, 18-84 yr old. PRSC was measured by the addition of excess human renal renin. ARC and TRC after trypsin activation were measured by adding sheep renin substrate; IRC was calculated by subtracting ARC from TRC. The active renin ratio was calculated as follows: ARC/TRC X 100%. PRA and PAC were measured by RIA. There were no significant changes in PRSC, TRC, IRC, and PRA to PAC ratio with aging. Both ARC and active renin ratio fell significantly with aging (r = 0.46 and P less than 0.01; and r = 0.54 and P less than 0.01, respectively). PRA and PAC also tended to decrease with aging (r = 0.35 and P less than 0.01; and r = 0.59 and P less than 0.01, respectively). A significant positive correlation was found between PRA and ARC (r = 0.72; P less than 0.001). PRA was also correlated with PAC. In conclusion, the age-related decrease in PRA is not due to the change in PRSC, but is mainly due to the fall in ARC. Decreased conversion of inactive to active renin might be responsible in part for the reduced ARC in the elderly.

Renin-angiotensin mechanisms in oral contraceptive hypertension in conscious rats.

Rats were placed on powdered chow containing either no additives (controls), mestranol (a synthetic estrogen), norethynodrel (a synthetic progestin), or both mestranol and norethynodrel. After 6 mo on these diets, catheters were placed in the carotid artery and jugular vein of each rat. An arterial blood sample was obtained for plasma renin activity (PRA), plasma renin concentration (PRC), and plasma renin substrate concentration (PRS). Mean arterial pressure was measured in each rat. The angiotensin II (ANG II) antagonist, [Sar1-Ile8]ANG II, was infused intravenously for 30 min while blood pressure was recorded. Rats treated with mestranol and/or norethynodrel had PRA and PRC values that were not different from the control rats; however, mestranol-treated rats and rats treated with mestranol plus norethynodrel had PRS values that were substantially (P less than 0.01) higher than the controls. Arterial pressures in rats treated with mestranol and with mestranol plus norethynodrel were significantly (P less than 0.01) elevated when compared with the controls and with the rats treated with norethynodrel alone. Infusion of the ANG II antagonist failed to alter arterial pressure in any of the groups of rats. These results indicated that, in the steroid combination found in the oral contraceptive Enovid, it is the estrogenic component that results in hypertension in this rat model. Also this study found no evidence that ANG II plays a role in maintaining the elevated arterial pressure following long-term treatment with mestranol in rats.

Multiple defects in the renin-angiotensin system in alloxan-diabetic kidney.

A defect in the renin-angiotensin system has been shown in diabetic patients and experimental animals, in particular with nephropathy or autonomic neuropathy. The mechanism for this low plasma renin activity (PRA) is poorly understood. In order to clarify this defect, the renin-angiotensin system was studied in alloxan-induced diabetic and age-match control mice. In diabetic animals, kidney renin activity (KRA) was significantly lower than that of the controls, while plasma renin substrate (PRS) concentration was slightly higher and PRA was normal. The amount of injected radiolabeled renin extracted by the kidney was normal, but the amount extracted by the liver was significantly decreased in diabetic animals. On the other hand, the degradation of the extracted renin by both the kidney and the liver was elevated as compared to the controls. This high degradation rate was accompanied by a slight increase in lysosomal protease activity in the kidneys. In in vivo studies, isoproterenol-induced PRA was 20-fold in control animals. In diabetics, isoproterenol-induced PRA was attenuated and rose only four- to fivefold over basal level. The angiotensin converting enzyme (ACE) activity in the kidney was significantly decreased in the diabetic state. It is concluded that there were multiple defects in the renin-angiotensin system in this diabetic model, namely, a depletion of renin storage with subsequent loss of maximal responsiveness to the adrenergic agonist in renin release, an elevation of intrarenal renin degradation together with a deficiency in ACE which would possibly lead to a decrease in intrarenal formation of angiotensin II.

Pathogenetic aspects of hypertension in Cushing's syndrome.

Abnormalities of the renin-angiotensin-aldosterone system (RAAS) were observed in hypertensive patients suffering from Cushing's syndrome. In 12 patients with different etiology of Cushing's syndrome renin substrate concentration and urinary-free cortisol, as well as the circadian rhythms of plasma cortisol, aldosterone and plasma renin activity were measured. Plasma renin substrate concentrations were found elevated in all but 1 patient, while plasma renin activity was elevated, normal or lowered. Plasma aldosterone values were found in the lower normal range. A physiological rhythm of cortisol secretion was not observed in any patient with Cushing's syndrome, while plasma aldosterone was secreted episodically mostly within the normal range. We conclude that changes of the RAAS may not be predominantly responsive for hypertension in Cushing's syndrome; other factors like circulating catecholamines are probably of greater importance for the pathogenesis of blood pressure elevation in hypercortisolemic patients.

Plasma renin concentration, activity and substrate in normal children.

Plasma renin concentration (PRC), activity (PRA) and substrate concentration (PRSC) were measured in 27 males and 31 female children aged 3 days to 14.5 years (median age 10 months). No sex difference between the three parameters was found and the data were therefore combined for boys and girls. Logarithmic transformation were used for all parameters. PRC, PRA and PRSC were significantly higher in children than in adults and were negatively correlated by age or body surface area. As expected, PRA was strongly positively correlated to PRC (r = 0.98, P less than 0.001) and to PRSC ( r = 0.55, P less than 0.001). From the second order partial correlation coefficients it is concluded that PRSC and PRC in children decrease with age or body surface area, and that PRA consequently also decreases. A negative feed-back regulatory mechanism between PRSC and PRC is suggested. Because of the decline in PRSC during childhood, it is recommended to measure PRC instead of PRA and to use age related reference values.

Direct radioimmunoassay for human renin substrate and its measurement in plasma from essential hypertensive patients, diabetic patients and pregnant women.

We homogeneously purified human renin substrate from outdated bank plasma and raised antibody against it. The antibody did not cross-react with angiotensin I, angiotensin II or synthetic tetradecapeptide at concentrations of up to 160 nmol, nor did it cross-react with up to 0.2 ml of plasma from rat, rabbit or sheep. It did, however, completely cross-react with human des-angiotensin I renin substrate. A direct radioimmunoassay for human renin substrate was developed using the antibody, and the minimum detectable value of renin substrate found to be 70 pg of protein. Plasma renin substrate concentrations of normal subjects, essential hypertensive patients, diabetic patients and pregnant women were measured by direct and indirect assays. Hypertensive patients had similar concentrations of plasma renin substrate to normal subjects, whereas diabetic patients had significantly lower plasma renin substrate concentrations (p less than 0.01). The direct assay always gave a higher value than the indirect assay, and the ratios of the two assays (direct assay/indirect assay) were similar in normal subjects, hypertensive patients, diabetic patients and pregnant women.

Effects of natural oestrogen therapy on blood pressure and renin-angiotensin system in normotensive and hypertensive menopausal women.

The blood pressure level and the renin-angiotensin system were investigated in 24 menopausal women (12 normotensive and 12 hypertensive) before, during and after six months of treatment with either oestradiol or trisekvens (sequential preparation containing oestradiol, oestriol and norethisterone acetate). In the normotensive women no significant alterations in systolic or diastolic blood pressure were found during treatment for six months. In the hypertensive women systolic blood pressure fell significantly during treatment with oestradiol as well as with trisekvens, while diastolic pressure did not change. All individual variations of blood pressure were small. The plasma concentrations of renin, angiotensin II and aldosterone remained unchanged during the treatments. A statistically significant increase in plasma renin substrate concentration was observed in all groups with the exception of the normotensive women treated with oestradiol. Menopausal symptoms in hypertensive women may safely be treated with natural oestrogens on the same indications as used for normotensive women.

The renin-angiotensin-aldosterone system in fulminant hepatic failure.

The relationship of the renin-angiotensin-aldosterone system to blood pressure and sodium homeostasis and to renal function was investigated serially in 12 patients with fulminant hepatic failure. The plasma concentrations of renin, angiotensin II, and aldosterone were, in most instances, markedly increased. Systolic blood pressure, which was often very low, showed a significant inverse relationship to the plasma renin concentration, suggesting that the marked stimulation of the system is a homeostatic response to hypotension. However, the plasma renin substrate concentration was markedly decreased, and the conversion of angiotensin II to inactive peptides increased, both of which may have severely limited the full 'expression' of the stimulated system. Renin and angiotensin II levels were both related to creatinine clearance, which was often reduced, but it is not clear as to which was cause and which effect. No relationship between the plasma aldosterone concentration and renal sodium excretion could be detected.

The renin-angiotensin system in panhypopituitarism: dynamic studies and therapeutic effects in Sheehan's syndrome.

To gain insight in the influence of the pituitary gland on the renin-angiotensin system plasma renin substrate (PRS) and the response of PRA to stimulation were studied in a homogeneous group of 20 female patients with the same etiology and degree of pituitary failure, before treatment (group P), after hydrocortisone substitution (group F), and after hydrocortisone and thyroid hormone treatment (group F + T). All patients were studied before and after each treatment by response to two stimulatory tests, acting through two different pathways; orthostasis test (O-T) and the furosemide test (Furo-T). Results were compared between groups, each patient serving as her own control, and with those obtained in a 12 healthy women control group (group C). The diet contained about 85 meq Na/day. Compared to group C (O-T response, 5.97 +/- 0.54 ng ml-1 h-1; Furo-T response, 6.71 +/- 0.82 ng ml-1 h-1; mean +/- SEM), PRA response to both tests was blunted in group P (O-T: 2.48 +/- 0.46, P less than 0.001; Furo-T: 3.02 +/- 0.53, P less than 0.001) and remained so in F (O-T: 2.18 +/- 0.40, P less than 0.001; Furo-T: 2.52 +/- 0.28, P less than 0.001), In group F + T, the response to both tests was greater than in P and F (O-T, 6.61 +/- 1.19; Furo-T, 4.36 +/- 0.44; 0.001 less than P less than 0.05). However, whereas the response to orthostasis is entirely normalized, the response to a diuretic remained significantly smaller than in group C (P less than 0.01). These improvements were observed without significant change in PRS concentration which remained low. We conclude that panhypopituitarism is accompanied by an altered renin angiotensin system. Basal levels of PRS and PRA are low and unresponsive to adequate stimulation. Whereas glucocorticoid therapy alone is without effect on this hyporeninism, addition of thyroid hormones completely normalized the response to orthostasis and significantly improved furosemide response.

Studies on the effect of mode of delivery on the renin-angiotensin system in mother and fetus at term.

Plasma renin substrate (PRS) and renin (PRC) concentrations were measured in the paired umbilical artery and vein blood of 54 babies and in the venous blood of 23 of their mothers at vaginal delivery. Similar samples were collected from 31 babies and their mothers at elective caesarean section. Fetal renin concentrations in both umbilical artery and vein blood were markedly increased at vaginal delivery compared with values at operative delivery. Renin substrate concentration was correlated with the length of second stage of labour. Umbilical vein PRC and PRS were greater than corresponding umbilical artery values at vaginal, but not at operative delivery, suggesting that some factor associated with delivery might stimulate the placenta to produce renin and renin substrate during vaginal delivery. Maternal and umbilical concentrations of both renin and renin substrate were unrelated, supporting the view that the maternal and fetal compartments are independent. It is suggested that hyperactivity of the renin-angiotensin system may be an integral part of the marked changes in cardiovascular homeostasis which occur at birth.