Clinical and experimental hypertension. Part B, Hypertension in pregnancy最新文献

In a longitudinal study of twelve normal pregnant women the base-line plasma values of 6-keto prostaglandin (PG)F1 alpha, the stable degradation product of prostacyclin, were determined. At the same time the capacity of their blood to produce prostacyclin was assessed using a stimulation test. When collagen is added to citrated whole blood there is a prompt rise in plasma 6-keto PGF1 alpha, which results from the synthesis of prostacyclin by leukocytes. These cells use cyclic endoperoxides in part coming from activated platelets and in part derived from endogenous substrate to produce prostacyclin. Both the base-line values and the capacity to produce prostacyclin fell significantly after 33 weeks of pregnancy. The decreased capacity to produce prostacyclin in the later stages of pregnancy may help account for the relatively diminished refractoriness to angiotensin II, characterizing the last two months of normal pregnancies.

Diurnal patterns of blood pressure and pressor hormones after 26 weeks gestation were compared in 10 normotensive women, 13 subjects with uncomplicated hypertension, and 8 with biochemical evidence of pre-eclampsia. 4 of the pre-eclamptics showed nocturnal hypertension. Levels of plasma renin activity fell progressively from 9 a.m. to midnight in all three groups, and were significantly lower in pre-eclampsia. Plasma angiotensin II levels fell during the day in normotensives and uncomplicated hypertensives, whereas pre-eclamptics showed loss of this pattern and significantly lower levels than the other groups. Free plasma norepinephrine levels fell during the day and to a similar extent in all three groups. A diurnal pattern for free plasma norepinephrine levels, with lower levels at midnight than during the day, was seen in normotensives and uncomplicated hypertensives but not in pre-eclamptics. Plasma norepinephrine sulphate levels rose from 9.00 a.m. to midnight in normotensives and uncomplicated hypertensives. This pattern was reversed in pre-eclamptics, including 3 of the 4 subjects with nocturnal hypertension. Plasma epinephrine sulphate levels rose progressively through the day, with no significant differences between groups. Failure of plasma angiotensin II or epinephrine levels to fall at night in pre-eclampsia may contribute to nocturnal hypertension in subjects with increased vascular reactivity. Suppression of plasma renin activity and angiotensin II levels suggests that perhaps as yet unidentified pressor mechanisms are involved in pre-eclampsia.

Pilot studies showed that, i.v. infusions of the renal prostaglandin A1 (PGA1) induced a triad of beneficial clinical responses in severe pre-eclampsia; the blood pressure became normotensive, renal function was markedly improved and labour was successfully induced. The present study was an attempt to develop a therapeutic schedule of PGA1 administration in severe toxemia. Twenty one cases of severe pre-eclampsia (in 3 equal groups) received i.v. infusions of PGA1 in a dose range of 0.1-0.5 microgram/kgm/min for 12 - 24 hours and the B.P., uterine activity and FHR were continuously monitored during and for 12 hours following the infusion period. The 0.1 microgram/Kgm/min dose for 12 hours was inadequate while 0.5 microgram/Kgm/min for 12 hours induced a good hypotensive response and the cases delivered within 48 hours but a post-infusion rebound in hypertension was observed. The dose of 0.5 microgram/Kgm/min for 24 hours appeared to be optimal in clinical terms since a satisfactory effect on B.P. was recorded and all the subjects delivered normal babies during the infusion period with minimal or no post-infusion rebound rise in B.P. This approach holds a major potential in the treatment of severe pre-eclampsia.

Two hundred and thirty-six pregnant women were referred for assessment and management of hypertension and/or renal disease. A Unit consisting of a physician, an obstetrician and a perinatologist jointly assessed each patient and advised on management. All patients were hospitalized and at bed rest. Drug therapy was clonidine hydrochloride or methyl dopa and in some patients a vasodilator was added. The decision to deliver was dictated by foetal maturity and wellbeing, in conjunction with maternal condition. There was no maternal mortality and the overall perinatal survival was 97%. The outcome of these pregnancies compares favourably with studies previously reported and reflect a successful approach to management of high risk hypertensive pregnancies.

A group of 29 women with previous pre-eclampsia/hypertension in pregnancy and 37 of their children were investigated. At follow-up 7-12 years later, all mothers had mild to moderate hypertension. The children had a significantly higher blood pressure than age and sex-matched controls. Intracellular Na+ in erythrocytes from the children was normal but potassium was significantly higher compared to normotensive controls. The history of maternal essential hypertension and previous pre-eclampsia/hypertension in pregnancy seems to indicate an increased risk for high blood pressure in children, evident before puberty.

Pharmacokinetic studies of the concentration of the beta 1-blocker metoprolol have been performed in maternal plasma, amniotic fluid, breast milk and the plasma of the newborn. The concentration of metoprolol in maternal plasma exceeds that in the amniotic fluid initially but not later on. The quotient between the metoprolol concentration in the venous maternal blood and the mixed cord blood at the time of delivery is at about 1. In the maternal plasma the metoprolol concentration will decline in a rapid way after the latest dose probably because of an increased clearance. Blood levels of metoprolol during the first postnatal hours will increase almost fourfold and are generally followed by a decrease over the next 15 hours. Active metabolites of metoprolol (alfa-OH-metoprolol and O-demethyl-metoprolol) are found in the urine of the newborn. The breast milk concentration of metoprolol is 3 times higher than in the maternal milk but the sucking newborn will only show very low or unmeasurable plasma levels between consecutive breast feeding periods in the majority of cases.

A retrospective study of urinary protein patterns, as determined by SDS-PAA-disc-electrophoresis was performed in 107 patients in third trimester of pregnancy because of preeclampsia. The aim was to determine whether the protein patterns allow a differentiation between nephropathies associated with genuine toxaemia of pregnancy and those in which toxaemia was superimposed on preexisting renal glomerular or tubular disease. The magnitude and type of proteinuria was related to the mean arterial pressure (MAP). 47% of all patients showed a mixed protein pattern independent of the MAP-severity. This form of proteinuria is probably associated with a genuine toxaemia of pregnancy. It was not possible to determine if pure glomerulopathies whose frequency rose with MAP, had already been present before pregnancy. In a third of the 22 patients followed-up post-partum pathological protein patterns or increased protein excretion was detected. This implies that 35% of the nephropathies were present before pregnancy. However, differentiation between preexisting and toxaemia associated nephropathy was not always possible. SDS-PAA-analysis of urinary protein should be carried out in earlier stages of pregnancy in cases of increasing MAP and proteinuria.

The main purpose of this study on rats was to examine the effect of pregnancy on experimental renal hypertension and cardiac size. Renal hypertension in the rats (RHR) was induced by standardized clamping of the left renal artery early in pregnancy (SRHR) or 4 weeks before mating (ERHR). As controls served non-pregnant RHR with the duration of hypertension matched to each above mentioned group, as well as non-pregnant and pregnant normotensive rats. Only 16% of the rats with renal artery clamping early in pregnancy (SRHR) developed hypertension in contrast to 41% of similarly operated non-pregnant rats and 56% of ERHR decreased their blood pressure to normal levels during pregnancy. Concerning left ventricular heart weight there was a slight increase in left ventricular weight during normal pregnancy in spite of a significantly reduced blood pressure. In both SRHR and ERHR an increased left ventricular heart weight was noticed during pregnancy even when arterial pressure was not increased. The present results suggest an antihypertensive effect of pregnancy and the existence of "trophic" influences and/or a volume induced adaptation of the heart causing an increased myocardial mass which is associated with pregnancy and partly independent of blood pressure influences.