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Biomedical subjects

F Broughton Pipkin

Publications and source records attributed to F Broughton Pipkin.

At least 145 records · Page 8Linked to original sources

Effect of the specific angiotensin antagonist (Sar1) (Ala8) angiotensin II on blood pressure and the renin-angiotensin system in the conscious pregnant ewe and fetus.

A direct relationship was found between maternal diastolic blood pressure and simultaneously measured angiotensin II (All) levels (P less than 0.001) in chronically cannulated pregnant ewes. The infusion of Saralasin to the ewe resulted in a dose-dependent fall in blood pressure (P less than 0.005), the magnitude of which was proportional to the initial All levels (P less than 0.025). Plasma renin and All levels rose significantly during the infusion. No consistent fetal effects were seen. The infusion of normal saline had no effect on blood pressure or hormone levels. Thus it seems likely that the renin-angiotensin system is involved with the maintenance of normal blood pressure in the pregnant sheep. Fetal blood pressure either fell significantly or was unchanged following direct infusion of Saralasin. This may be related to development of the beta-adrenergic nervous system. The renin-angiotensin system may be more important in cardiovascular homeostasis in the immature than in the adult animal.

Aldosterone↗

Sequential changes in the human renin-angiotensin system following delivery.

Plasma renin activity and concentration and angiotensin II concentration have been measured serially in six normotensive primigravidae and in four mildly hypertensive patients in the four immediately following normal delivery. In normotensive patients, both renin and angiotensin II levels fell sharply over the first two hours to levels within the non-pregnant range, with a subsequent rise to levels, similar to those found in late pregnancy. Changes in the mildly hypertensive patients were smaller, and somewhat slower. It is suggested that the initial fall represents clearance of a renin of fetoplacental origin and that the subsequent rise may be a release from feedback suppression of renal renin synthesis.

Angiotensin II↗

Placental transfer of a large angiotensin fragment in the guinea pig.

Angiotensin II (AII) levels are usually higher in the fetal than in the maternal circulations. Radioiodinated AII has been used to establish whether or not this hormone crosses the placenta from the fetus to the mother in the pregnant guinea pig. No intact radioiodinated AII was found to have crossed in any of 13 experiments. A single radioiodinated AII fragment was found in 10 of these experiments. This ran as (des-(Asp1 Arg2 Val3)) in one solvent, but this could not be confirmed when a different solvent was used. The results support the hypothesis, previously based on indirect evidence, that AII does not cross the placenta.

Angiotensin II↗

The effect of prostaglandin E2 on the cardiovascular response to angiotensin II in pregnant rabbits.

The rise in arterial blood pressure in response to angiotensin II was studied in the last third of pregnancy in rabbits. The response was compared with that of pregnant rabbits during infusion of prostaglandin E2 and F2alpha. Prostaglandin E2 significantly diminished the rise in diastolic pressure in response to angiotensin II. Prostaglandin F2alpha did not alter the response. Intravenous indomethacin elevated the blood pressure and caused an absolute increase in the pressor response. It did not mediate a change in the percentage rise in blood pressure in response to angiotensin II.

Angiotensin II↗

A study of factors affecting blood pressure and angiotensin II in newborn infants.

Blood pressure has been measured using the Doppler ultrasonic technique in 144 infants in the first 11 days of life. Venous angiotensin II levels measured by radioimmunoassay were determined in 75 of these babies. Highly significant correlations were found between systolic blood pressure and gestational age and body weight. AII was inversely related to blood pressure and significantly related to birth weight. Babies with respiratory distress were found to be significantly hypotensive and to have markedly raised AII levels.

Angiotensin II↗

Factors affecting angiotensin II concentrations in the human infant at birth.

1. A radioimmunoassay for the measurement of angiotensin II in 1 ml of plasma has been developed and used to measure angiotensin II in maternal peripheral, cord venous and cord arterial blood in 45 patients at delivery. 2. In babies delivered vaginally, cord venous and cord arterial concentrations of angiotensin II were significantly higher than maternal venous blood concentrations. There was a significant relationship between both cord venous and cord arterial concentrations and maternal concentrations of angiotensin II. 3. Cord venous concentrations of angiotensin II were significantly greater than those in cord arterial blood in babies delivered vaginally but not in those delivered by lower-segment Caesarean section. This suggests the possibility that, during labour, the placenta may contribute to foetal concentrations of angiotensin II. 4. Maternal and cord venous concentrations of angiotensin II were significantly higher in patients with hypertensive disease of pregnancy than in those who had remained normotensive throughout pregnancy. 5. Cord venous concentrations of angiotensin II increased significantly with increasing duration of the second stage of labour.

Angiotensin II↗

The fetal renin-angiotensin system in normal and hypertensive pregnancy.

Plasma angiotensin II was measured in the umbilical cord arterial and/or venous blood of 54 babies delivered vaginally and in 12 delivered by elective lower segment cesarean section. Angiotensin II was also measured in the peripheral venous blood of 51 of the mothers. Mean angiotensin II levels at delivery were higher in the cord venous blood of infants born to hypertensive than to normotensive mothers. Cord venous angiotensin II levels were always higher than those of the mother and there was a strongly positive relationship between maternal and fetal angiotensin II. The duration of the second stage of labor was found significantly to affect fetal angiotensin II levels, prolonged labor being associated with high levels. When this was taken into account, there was a highly significant positive relationship between the body weight of the infants and cord venous angiotensin II levels. There was an inverse relationship between cord venous pH and angiotensin II levels. Babies delivered by lower segment cesarean section had much lower angiotensin II levels than those delivered vaginally. The levels were, however, twice as high as those in the nonpregnant adult.

Angiotensin II↗

Changes in the renin-angiotensin system in normotensive and hypertensive women during pregnancy and parturition.

Plasma renin activity, plasma renin concentration and plasma angiotensin II were measured in 18 primigravid women and 17 multiparous women between 37 and 42 weeks of gestation. Seven of the primigravid and seven of the multiparous women were admitted to hospital because they developed hypertension during pregnancy. In the primigravid group, the mean angiotensin II level was significantly higher in the hypertensive than in the normotensive women. A highly significant correlation was found between diastolic blood pressure and plasma angiotensin II levels. Although a similar trend was seen in the multiparous women, there was a wide scatter of values and the relationship between diastolic blood pressure and plasma angiotensin II was not significant. No correlation could be established between plasma renin concentration and angiotensin II levels. However, there was a trend towards a negative correlation between plasma renin activity and plasma angiotensin II, suggesting that high angiotensin levels may suppress renal renin release. The influence of parturition on plasma angiotensin II levels was investigated in 12 women. Maternal plasma angiotensin II levels were significantly higher in the second stage of labor than in women delivered by elective cesarean section.

Angiotensin II↗

Changes in the renin-angiotensin system in primigravidae with hypertensive disease of pregnancy.

Plasma renin concentration, renin activity and angiotensin II (AII) have been studied in 35 primigravidae at or near term immediately prior to surgical induction of labour. A highly significant positive correlation was established between diastolic blood pressure at the time of sample collection and plasma AII. This relationship was observed over the range of diastolic pressure studied irrespective of the diagnosis made at the time of admission to hospital. In patients with hypertension, a significant negative relationship was established between plasma renin concentration and renin activity and AII. Furthermore, plasma AII levels were higher for a given plasma renin activity or plasma renin concentration in the hypertensive women than in the normotensive group. These findings suggest that the renin-angiotensin system is actively involved in hypertensive disease of pregnancy and that suppressed levels of renin concentration and activity may result from elevated angiotensin levels. It is suggested that the utero-placental complex may be the source of the elevated AII levels.

Adolescent↗

Renin and angiotensin-like levels in foetal, new-born and adult sheep.

1. Plasma renin (measured as rate of formation of angiotensin I ng/ml.hr(-1) in the presence of added substrate at pH 7.5 and 37 degrees C) was much lower in recently nephrectomized foetal, new-born and older lambs than in intact siblings or other similar lambs.2. Angiotensin II-like concentrations were measured using a superfusion technique in an extracorporeal circuit. Resting concentrations in acute experiments under anaesthesia were deduced by comparison of carotid blood of intact lambs with that from recently nephrectomized lambs.3. Angiotensin II-like activity (mean +/- S.E. of mean, 315 +/- 117 pg/ml.) was readily detectable in foetal blood at 123-138 days gestation. The highest concentrations (mean +/- S.E. of mean 839 +/- 96 pg/ml.) were found in lambs less than 8 hr old, delivered vaginally. The lowest concentrations of angiotensin II-like activity occurred in lambs delivered by Caesarean section (mean +/- S.E. of mean < 123 +/- 12 pg/ml.). Concentrations declined with post-natal age.4. Hypovolaemia as a result of haemorrhage evoked an increase in angiotensin II-like concentrations in foetus, new-born lambs and adult sheep. The greatest increase of angiotensin-like concentrations was seen in new-born lambs. This rise was associated with increase of plasma renin.5. The rise of arterial pressure during bilateral carotid occlusion in new-born lambs was accompanied by an increase of angiotensin II-like concentration.6. It is concluded that the renin-angiotensin system is functional and can be stimulated during intra-uterine life. The increase of angiotensin II-like concentration following parturition is probably transient and associated with the trauma of delivery. This contrasts with observations made in the rabbit which suggest that full functional maturity of the renin angiotensin system is delayed until the second week of life.

Angiotensin II↗

Factors influencing plasma renin and angiotensin II in the conscious pregnant ewe and its foetus.

1. Plasma renin (measured in the presence of additional substrate) was significantly higher (10.7 +/- 1.1 S.E. of mean ng/ml.hr) in foetal lambs of 111-144 days gestation age (full term 147 days) than in their mothers (1.5 +/- 0.2 ng/ml.hr S.E. of mean, P < 0.001) but plasma angiotensin II concentrations were in the same range (ewe 47.3 +/- 6.6 S.E. of mean, foetus 47.4 +/- 14.1 S.E. of mean pg/ml.). The endogenous velocity of renin production by foetal plasma was also greater than that of maternal plasma.2. Foetal plasma [Na(+)] (137 +/- 0.8 S.E. of mean m-equiv/l.), was lower than that in the ewe (142 +/- 1.5 m-equiv/l. S.E. of mean, P < 0.01).3. Foetal plasma renin in lambs of less than 120 days gestation was lower (9.2 +/- 2.7 S.E. of mean ng/ml.hr) than that in lambs of over 130 days gestation (12.6 +/- 2.6 ng/ml.hr S.E. of mean, P < 0.01). Foetal plasma [K(+)] (3.8 +/- 0.1 S.E. of mean m-equiv/l.) was also lower in lambs of less than 120 days gestation than in those over 130 days (4.1 +/- 0.1 S.E. of mean m-equiv/l., P < 0.001).4. When small volumes of blood (</= 3% of blood volume) were withdrawn from foetal lambs, plasma renin increased. The% increase of plasma renin in hypoxaemic foetal lambs was significantly less (P < 0.05) than in control lambs. At the end of 60 min hypoxaemia, arterial pressure and plasma [K(+)] were significantly higher in hypoxaemic than in control foetal lambs.5. During foetal hypoxaemia, plasma angiotensin II concentration increased concurrently with plasma renin.6. Bilateral nephrectomy was performed in two foetal lambs. Plasma renin fell to very low levels and angiotensin II became undetectable.7. Adrenaline ( approximately .0.42 mug/min.kg I.V.) infused into the foetus did not alter foetal plasma renin. When adrenaline was infused into the ewe ( approximately 0.26 mug/min.kg) maternal plasma renin increased. Maternal infusion of adrenaline raised foetal plasma renin significantly more (P < 0.05) than foetal infusion.8. It is concluded that the foetal kidney is the major source of foetal renin in the last quarter of gestation and that renin release is stimulated by very small reductions of blood volume. Hypoxaemia does not augment renin release and cannot be responsible for high levels of renin and angiotensin associated with vaginal delivery.

Angiotensin II↗