Toshimitsu Nakamura

Effect of calcium supplementation on the vascular sensitivity to angiotensin II in pregnant women

Pregnant women destined to develop pregnancy-induced hypertension lose refractoriness to the pressor effects of infused angiotensin II. The effect of calcium supplementation on the vascular sensitivity to angiotensin II was investigated in pregnant women. We administered orally 600 mg of calcium L-aspartate daily to 22 pregnant women from 20 weeks of gestation to delivery. The values for the effective pressor dose of angiotensin II in the calcium-supplemented women were compared with those in 72 nonsupplemented pregnant women. The vascular sensitivity was significantly decreased after calcium supplementation. The values for the effective pressor dose of angiotensin II in the calcium-supplemented patients were 18.1 +/- 1.2 ng/kg/min at 20 weeks of gestation, 32.2 +/- 2.6 ng/kg/min at the twenty-sixth week, 41.1 +/- 3.4 ng/kg/min at the thirtieth week, and 25.9 +/- 2.9 ng/kg/min at the thirty-sixth week (mean +/- SEM), while those in the nonsupplemented patients were 17.3 +/- 1.2, 17.7 +/- 1.6, 17.6 +/- 1.2, and 15.0 +/- 1.6 ng/kg/min, respectively. Assessment of the changes in the effective pressor dose of angiotensin II in the individual patients indicated that the percentile changes from 20 weeks of gestation in the calcium-supplemented patients were also significantly greater than those in 22 nonsupplemented patients. These findings suggest that calcium supplementation tends to reduce the vascular sensitivity in pregnancy. The present dosage of calcium did not affect the blood chemical parameters and did not reduce the blood pressure. The incidence of pregnancy-induced hypertension in the calcium-supplemented patients was 4.5%, which was smaller than that (21.2%) in the nonsupplemented patients. Although there is no clear explanation of the mechanisms involved in such an effect of calcium, the present results do provide evidence to support the idea that oral calcium intake can prevent the onset of pregnancy-induced hypertension.

The influence of labor on thrombotic and fibrinolytic systems

Plasma fibrinopeptide A, thrombin-antithrombin III complexes, tissue-plasminogen activator and alpha 2-plasmin inhibitor-plasmin complexes were measured early in the first stage of labor, in the second stage of labor and at 15 min after placental separation. Fibrinopeptide A and thrombin-antithrombin III complex levels did not change from the first to the second stage of labor but increased significantly after placental separation. There was a significant increase of the tissue-plasminogen activator level between the early first stage of labor and the second stage of labor, and it remained high after placental separation. A significant increase in the level of plasma alpha 2-plasmin inhibitor-plasmin complexes was observed after placental separation. These findings suggest that activation of the thrombotic system occurs at the time of placental separation and that activation of the fibrinolytic system begins during labor before placental separation to compensate for the hypercoagulable state which develops at the time of delivery.

The blood pressure response to infusions of angiotensin II during normal pregnancy: Relation to plasma angiotensin II concentration, serum progesterone level, and mean platelet volume

Objective: This study is a survey of the determinants of refractoriness to the pressor effects of angiotensin II during normal pregnancy. Study Design: In 25 normal pregnant women, the effective angiotensin II pressor dose was determined 88 times from the twenty-fifth to the thirty-second week of gestation. Immediately before the angiotensin II infusion, blood samples were collected and measured for plasma angiotensin II concentration, serum progesterone level, platelet count, and mean platelet volume. Results: The effective pressor dose had a significantly positive correlation with plasma angiotensin II concentration and serum progesterone level and a negative correlation with mean platelet volume. Conclusion: The pregnancy-associated refractoriness to angiotensin II is physiologically determined, at least in part, by the elevated circulating levels of endogenously produced angiotensin II and by the progesterone produced by the placenta, whereas platelet activation attenuates the relative refractoriness during normal pregnancy.

Effects of pregnancy and hormone treatments on pressor response to angiotensin II in conscious rats.

Pressor responses to graded doses of angiotensin II in conscious rats were significantly reduced on days 13 and 19 of pregnancy compared with those in nonpregnant rats. To study the hormonal regulation of this altered pressor response to angiotensin II during pregnancy, we administered estradiol, progesterone, and human chorionic gonadotropin to nonpregnant rats. In ovariectomized rats no effect of estradiol on the pressor response to angiotensin II was found, but injections of progesterone with or without estradiol pretreatment significantly reduced the pressor response to angiotensin II. In intact rats human chorionic gonadotropin induced elevation of endogenous progesterone levels, followed by a significant decrease in the pressor response to angiotensin II. Injection of estradiol after human chorionic gonadotropin pretreatment produced a significant elevation in the pressor response to angiotensin II. These findings indicate that the decrease in angiotensin pressor response in pregnant rats is mediated mainly by progesterone rather than by estrogen.

Usefulness of the urinary microalbumin/creatinine ratio in predicting pregnancy-induced hypertension.

In 199 normotensive pregnant women at 20 and 30 weeks of gestation, a fasting urinary albumin/creatinine ratio (FU Alb/Cr) was evaluated to predict pregnancy‐induced hypertension (PIH). FU Alb/Cr in patients destined to develop PIH was significantly high compared to that in normotensive women. When FU Alb/Cr of more than 16 was considered to represent a positive test result, the negative predictive value was 94% and 96%, respectively. FU Alb/Cr is a useful screening tool for PIH.

Effects of Pregnancy and Estrogen on the Angiotensin II Pressor Response of the Rabbit Using Serial Systolic Blood Pressure Measurement in the Ear

Serial systolic blood pressure measurements were made in order to assess the effects of pregnancy and estrogen on the angiotensin II pressor response of the rabbit. The systolic blood pressure of the ear in 5 pregnant rabbits did not change throughout the gestational period, being compatible with that in 14 nonpregnant rabbits. However, vascular resistance to infused angiotensin II (over 13.1 ng/kg/min required to elicit a pressor response of 20 mmHg in systolic pressure) was demonstrated as early as the 10th day of pregnancy, and maximum mean resistance occurred on the 20th day: the mean pressor dose required was 34.5 ± 3.6 ng/kg/min (mean ± S.D.). In a separate series, vascular resistance in castrated rabbits was demonstrated as early as the 10th day of estrogen administration, reached a maximum at the 4th week, and then gradually decreased to the control level (pretreatment, 10.5 ± 2.5 ng/kg/min; 10 days, 18.9 ± 2.3 ng/kg/min; 4 weeks, 32.4 ± 5.4 ng/kg/min; 10 weeks, 18.3 ± 3.6 ng/kg/min; and 24 weeks,...

Vasopressor activity in incubated plasma of normal and hypertensive pregnant women

The pressor activity generated in incubated plasma of nonpregnant, normal pregnant, and hypertensive pregnant women was measured by means of a sensitive bioassay technique. It was found that the plasma of normal pregnant women generated significantly higher amounts of active pressor principle than the plasma of nonpregnant women. The plasma of hypertensive pregnant women generated significantly lower amounts of active pressor principle than the plasma of normal pregnant women. Plasma obtained from the antecubital vein revealed no difference in pressor activity compared to plasma collected from the uterine vein at the time of cesarean section. These data suggest that active pressor principle is not involved in the pathogenesis of pregnancy-induced hypertension and that the pregnant uterus is not the source of active pressor principle.

Increased Pressor Response to Angiotensin II after Stricture of the Abdominal Aorta in Pregnant Rabbits

The abdominal aorta of 7 pregnant rabbits was treated below the renal arteries on the 21st day of pregnancy, producing a stricture which reduced the lumen to 2.0 mm in diameter. The pressor response to angiotensin II was assessed by measuring the systolic blood pressure of the ear using a Grant-Rothschild capsule. After stricture of the abdominal aorta, the systolic blood pressure in pregnant rabbits was not statistically different from that of sham operated rabbits. However, a significant increase in vascular reactivity to infused angiotensin II was demonstrated during the remaining gestational period.These findings suggest that interference with the blood supply of the pregnant uterus is an important factor in determining the vascular reactivity to angiotensin II in pregnant rabbits

The blood pressure response to infusions of angiotensin II during normal pregnancy: Relation to plasma angiotensin II concentration, serum progesterone level and mean platelet volume

OBJECTIVE This study is a survey of the determinants of refractoriness to the pressor effects of angiotensin II during normal pregnancy. STUDY DESIGN In 25 normal pregnant women, the effective angiotensin II pressor dose was determined 88 times from the twenty-fifth to the thirty-second week of gestation. Immediately before the angiotensin II infusion, blood samples were collected and measured for plasma angiotensin II concentration, serum progesterone level, platelet count, and mean platelet volume. RESULTS The effective pressor dose had a significantly positive correlation with plasma angiotensin II concentration and serum progesterone level and a negative correlation with mean platelet volume. CONCLUSION The pregnancy-associated refractoriness to angiotensin II is physiologically determined, at least in part, by the elevated circulating levels of endogenously produced angiotensin II and by the progesterone produced by the placenta, whereas platelet activation attenuates the relative refractoriness during normal pregnancy.

Increase of plasma tissue-plasminogen activator antigen levels after induced abortion

SummaryWe previously reported that plasma thrombotic activity is transiently increased immediately after induced abortion. However, changes in the fibrinolytic system have not vet been studied. Plasma tissue-plasminogen activator (t-PA) antigen levels were studied before and after abortion induced during the first trimester of pregnancy. Compared with the preoperative level (1.68 ± 0.15 ng/ml), t-PA level was significantly increased (2.78 ± 0.55 ng/ml, p<0.01) 15 min after the induced abortion, while it almost returned to the preoperative values (2.09 ± 0.40 ng/ml) 2h later. This finding suggests that fibrinolytic activity is transiently increased immediately after the induced abortion, acting as a defense mechanism against thrombosis.We previously reported that plasma thrombotic activity is transiently increased immediately after induced abortion. However, changes in the fibrinolytic system have not yet been studied. Plasma tissue-plasminogen activator (t-PA) antigen levels were studied before and after abortion induced during the first trimester of pregnancy. Compared with the preoperative level (1.68 +/- 0.15 ng/ml), t-PA level was significantly increased (2.78 +/- 0.55 ng/ml, p less than 0.01) 15 min after the induced abortion, while it almost returned to the preoperative values (2.09 +/- 0.40 ng/ml) 2h later. This finding suggests that fibrinolytic activity is transiently increased immediately after the induced abortion, acting as a defense mechanism against thrombosis.