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Biomedical subjects

F Broughton Pipkin

Publications and source records attributed to F Broughton Pipkin.

158 records · Page 9Linked to original sources
PubMed1971

Angiotensin II-like activity in circulating arterial blood in immature and adult rabbits.

1. Angiotensin II-like activity was estimated from the contraction of the rat ascending colon superfused with arterial blood in an extracorporeal circuit. The colon was calibrated by infusion of synthetic angiotensin II amide (Hypertensin, CIBA Ltd).2. Resting levels of angiotensin II-like activity were obtained by comparison of the length of a rat colon preparation superfused alternately with blood from an intact and from a nephrectomized rabbit.3. The resting levels of angiotensin II-like activity reached a maximum value of about 1.6 ng/ml. at 10-14 days of age, and thereafter declined to the adult value of 0.23 ng/ml. Rabbits of less than 100 g body weight had resting levels in the same range as adults.4. Removal of 25% of the calculated blood volume induced five times greater increments in arterial angiotensin II-like activity in immature than in adult rabbits (1.68 +/- 0.26 S.E. of mean ng/ml. compared with 0.34 +/- 0.08 S.E. of mean ng/ml.).5. No evidence was obtained that the high levels of angiotensin II-like activity encountered in immature rabbits were attributable to a slower rate of inactivation of angiotensin by tissues.6. The pronounced activity of the renin-angiotensin system demonstrated by these experiments in immature rabbits especially during haemorrhage is consistent with the suggestion that this system is of particular importance in cardiovascular control in early life.

Age Factors↗
PubMedDate not supplied

Hypertension in pregnancy.

Hypertension arising during pregnancy remains one of the two most frequently-cited causes of maternal death in the UK. In some cases, pregnancy is unmasking underlying hypertension, which manifests itself in later life. Pregnant women who develop de novo proteinuric hypertension (pre-eclampsia, PE) can share many risk factors with patients with the metabolic syndrome, such as obesity, dyslipidaemia and insulin resistance. However, more than half the women who develop PE remain normotensive thereafter. There is a genetic component(s) to the disease, but it is most improbable that there is a 'PE gene'. Rather, there are factors such as genetically-determined thrombophilias which are predisposers but not prerequisites. Impaired placentation is a feature, with inadequate invasion of the spiral arteries by syncytiotrophoblast and poor remodelling. However, similar features are found in association with non-hypertensive fetal growth restriction. Prospective studies have suggested a hyperdynamic circulation in early pregnancy, with cardiac output only falling in established disease. Baroreflex sensitivity is decreased in normal pregnancy, and still further decreased in established PE. Activation of endothelial cell function antedates the clinical diagnosis, and has features in common with atherosclerosis. Dyslipidaemia is common in PE and, via oxidation of susceptible lipids, may contribute to endothelial activation. Oxidative 'stress' is increased in PE, perhaps through a variant of the hypoxia-reperfusion phenomenon in the developing intervillous spaces. Such early changes might then lead to the clinically-evident syndrome in susceptible women. PE is a protean, multisystem, multifactorial disease, the causes of which are only slightly less enigmatic than a decade ago.

Baroreflex↗
PubMedDate not supplied

The localization and expression of the renin-angiotensin system in the human placenta throughout pregnancy.

All the components of the renin-angiotensin system (RAS), including the AT(1)receptor, have previously been shown to be present in the human term placenta. However, the presence of the RAS components has not been fully investigated in the human placenta throughout pregnancy. The aim of this study was to examine the localization of the angiotensin receptors AT(1)and AT(2)using immunocytochemistry and the expression of prorenin, angiotensinogen and the AT(1)and AT(2)receptor mRNA using RT-PCR in the human placenta in the first, second and third trimesters of pregnancy. Localization of the AT(1)receptor was shown throughout gestation in the syncytiotrophoblast, cytotrophoblast, Hofbauer cells and the fetal vascular endothelium. Expression of mRNA for prorenin, angiotensinogen and the AT(1)receptor was shown in the placenta throughout gestation. However, localization or mRNA expression of the AT(2)receptor was not detected in any of the placental samples studied. These results clearly show the expression of a majority of the components of the RAS in the placenta from early gestation onwards. Therefore, these results suggest that the RAS may have a role in the human placenta throughout gestation.

Angiotensin II↗
PubMedDate not supplied

Studies on the effect of normal labour and obstetric analgesia on maternal and cord venous plasma angiotensin converting enzyme activity in primigravidae.

A spectrophotometric (optimized) assay of plasma angiotensin converting enzyme (ACE) activity was carried out in the plasma of primigravid subjects before and after labour; and in the plasma of cord various blood samples obtained from these subjects. The assay was based on the calorimetric determination of hippurate with cyanuric chloride/dioxan reagent, as described by Hurst and Lovell-Smith. The coefficient of variation (CV) for this method during the assay ranged from 7.36% to 8.19% and from 9.20% to 9.79% for the hippurate standards and the control plasma samples respectively. The mean +/- SD of maternal plasma ACE activity before labour and at delivery in the primigravid subjects were 22.23 +/- 4.17 and 16.44 +/- 1.71 units-1 min-1 respectively; while the corresponding value of enzyme activity in the cord venous plasma for these subjects was 15.71 +/- 1.61 unit-1 min-1. Normal labour did not appear to alter significantly the level of maternal and cord venous plasma ACE activity. It would appear that epidural analgesia has a significant effect on the level of maternal plasma ACE activity during labour (x2 = 12.59 P less than 0.05), but not on the cord venous plasma ACE activity.

Analgesia, Epidural↗
PubMedDate not supplied

Studies on the effects of nitrendipine on oxytocin, angiotensin II and ergometrine-induced contraction of pregnant human myometrium in vitro.

The effects of nitrendipine, a Calcium channel antagonist, on stimulated contractions of 72 tissue strips of pregnant human myometrium was studied. The agonists used were oxytocin, angiotensin II (AII) and ergometrine maleate. The concentration: response curves for the contractile effects on these agonists on the myometrial tissue strips were initially established in three separate but identical experiments (n = 24 in each group) over a predetermined optimal concentration range of each of the agonists. Contractions were recorded isotonically against a fixed tension of 500mg using microtorque technique. The curves were then re-established, for each agonist, in the absence and in the presence of 10(-9)M nitrendipine. The agonists consistently contracted the myometrial tissues in a dose-dependent manner during the establishment of the initial curves. The overall initial EC50 for the oxytocin treatment group was 6.4 x 10(-10)M, while the corresponding EC50s for the AII, and ergometrine treatment groups were 5.9 x 10(-11) and 4.0 x 10(-8)M respectively. Nitrendipine significantly blunted the myometrial tissue response to oxytocin. The EC50 of the oxytocin control group was significantly different from similar group treated with nitrendipine. (9.0 x 10(-10)M for the control, as compared with 8.3 x 10(-7)M for the nitrendipine treatment group p less than or equal to 0.05). Nitrendipine did not significantly influence the myometrial tissue response to AII or ergometrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMedDate not supplied

Studies on the response of isolated human chorionic plate artery strips to angiotensin II in normal pregnancy and in pregnancy induced hypertension.

A six point concentration: response curves for the contractile effect of angiotensin II (AII) on helically-cut strips of human chorionic plate arteries were established at final concentration of between 10(-14) M to 10(-9) M. The tissues were obtained from the placentae of women who had normotensive pregnancy and from those who had pregnancy-induced hypertension (PIH). A total of 24 chorionic plate artery strips were studied. The responses of the tissues from the normotensive and hypertensive pregnant subjects to physiological concentrations of AII (10(-14)-10(-13)M) were very similar. The overall EC50s were 8.0 x 10(-13) and 4.5 x 10(-13)M for the normotensive and the hypertensive tissues respectively. However, at higher concentrations of AII (10(-12) M and above) the artery strips from the PIH subjects were significantly more sensitive to AII than the tissues from the normotensive subjects (P less than or equal to 0.05). It is suggested that vasospasm and hypersensitivity characteristic of maternal vascular response to angiotensin II, in pregnancy induced hypertension, also occur in the placental vascular system.

Adult↗
PubMedDate not supplied

Differential sensitivity of human nonpregnant and pregnant myometrium to calcitonin gene-related peptide.

OBJECTIVES: Calcitonin gene-related peptide (CGRP) is a smooth muscle relaxant with potent vasodilating properties. To investigate its inhibitory effects on human myometrial contractions, we obtained excised human myometria from term pregnant, with and without spontaneous labor, and nonpregnant patients. METHODS: Myometrial strips were mounted in tissue baths in which contractile activity was recorded. Spontaneously contracting tissues in vitro were exposed to increasing concentrations of CGRP (10(-11)-10(-7) mol/L). Tissues without spontaneous contractions were induced to contract with either oxytocin or KCl before being exposed to CGRP. The IC25 (CGRP concentration required to inhibit contractility by 25%) was used as comparison between groups. RESULTS: Tissues with spontaneous or oxytocin-induced in vitro contractions responded equally to CGRP relaxation. Tissues induced to contract with KCl in vitro required approximately 2000 times more CGRP for equal relaxation. In tissues with spontaneous or oxytocin-induced in vitro contractions, those from pregnant unlabored patients were 60 times more sensitive to CGRP than those from pregnant labored or nonpregnant patients. The letter two groups responded equally to CGRP. CONCLUSIONS: The sensitivity of myometrial tissues to CGRP relaxation in vitro is increased from the nonpregnant to the pregnant term state. This increased sensitivity is lost once patients develop spontaneous term labor. The relative ineffectiveness of CGRP in relaxing KCl-induced in vitro contractions probably reflects its known mechanism of action, namely the hyperpolarization of cell membrane potentials via activation of membrane potassium channels.

Adult↗