Abstract-We tested the hypothesis that women with idiopathic fetal growth restriction (FGR) or preeclampsia (PE) have lower concentrations of some water-retaining hormones, such as aldosterone and estradiol, either preceding or concomitant with the onset of the reduced plasma volume described in these women. Plasma volume and serum concentrations of estradiol, progesterone, and aldosterone were measured serially at monthly intervals in 135 pregnant women from week 10 until term. Twenty-three developed idiopathic FGR, 17 had PE, and 95 remained normotensive and delivered normal-size infants (controls). Changes over time for each variable were studied using mixed models.Maternal age, parity, and weight/height at term were similar in all of the groups. Birth weight, body length, and ponderal index were lower in FGR and PE than in controls. Plasma volume increased throughout pregnancy in controls but was lower in FGR and PE from week 14 to 17 until term. Aldosterone values were lower in PE from week 26 to 29 onwards and in FGR after week 34. Progesterone concentrations were higher in PE than either control or FGR from week 18 to 21 until term. In contrast, FGR pregnancies had reduced progesterone and estradiol concentrations after week 34. Progesterone:estradiol ratio was significantly higher only in the PE group. In mothers with idiopathic FGR or PE, less expansion in plasma volume occurred before alterations in hormonal concentrations. We speculate that the early rise in progesterone may have a pathogenic role in the development of preeclampsia. Key Words: blood Ⅲ aldosterone Ⅲ preeclampsia Ⅲ estrogen P reeclampsia (PE) and fetal growth restriction (FGR) are frequent disorders of pregnancy and a leading cause of prenatal morbidity and mortality. In near-term pregnant women with either PE or FGR, we demonstrated lower plasma volume expansion, reduced cardiac output, and an increased total peripheral vascular resistance when compared with normotensive women who gave birth to normal-size infants. 1-3 Volume expansion during normal pregnancy seems to be secondary to renal and systemic vasodilatation that would activate the renin-angiotensin-aldosterone system that, in turn, would cause renal sodium and water retention. 4 -6 Estrogen production may also have a role in plasma volume expansion by stimulating hepatic angiotensinogen synthesis. 5,7 According to this proposed pathway for volume expansion, in the present study we tested the hypothesis that women with PE or FGR would have lower serum aldosterone and estradiol concentrations either preceding or concomitant with the onset of the reduced plasma volume. We measured plasma volume and hormonal concentrations in initially healthy pregnant women from weeks 10 to 13 until near term. After delivery, we compared the time course of these changes in control, FGR, and PE women. MethodsParticipants were women attending 2 prenatal clinics of the Southeastern Health Service of Santiago, Chile (Alejandro del Río and La Granja). These women belonged to a low-income population ...

We conducted the present study to investigate whether the vasodilator nitric oxide plays a role in plasma volume homeostasis during pregnancy. Pregnant Sprague-Dawley rats were randomly assigned to a control group (n = 18) or to groups receiving 0.69 mmol/L (n = 11) or 1.7 mmol/L (n = 14) N omega-nitro-L-arginine, a competitive inhibitor of nitric oxide synthetase, from gestational days 7 through 21. On day 20 systolic pressure was measured. On day 21 blood samples were taken for plasma volume, hematocrit, and hormonal measurements. Fetal and placental weights also were determined. Systolic pressure was significantly higher in experimental rats (101 +/- 6 and 115 +/- 6 mm Hg in the 0.69 and 1.7 mmol/L groups, respectively) than in controls (79.7 +/- 7.5 mm Hg), and plasma volume was lower (18.4 +/- 1.1 and 17.1 +/- 0.5 mL) than in controls (21.5 +/- 0.8 mL). Both experimental groups had increased hematocrit levels. Plasma renin activity was significantly lower in the experimental groups (11.5 +/- 3 and 7.2 +/- 1.5 ng angiotensin I/mL per hour) than in controls (21.9 +/- 2.7 ng angiotensin I/mL per hour); however, no changes were observed in aldosterone levels. Experimental groups had lower fetal weight (4.6 +/- 0.1 and 5.1 +/- 0.1 g) than controls (5.5 +/- 0.1 g). In addition, fetal hindlimb hypoplasia was observed in the experimental groups. In conclusion, the present data indicate that long-term N omega-nitro-L-arginine administration to pregnant rats leads to increased blood pressure, reduced plasma volume expansion, lower plasma renin activity, and fetal growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Abstract-Pregnant women with preeclampsia have increased serotonin levels, suggesting a possible role of this amine in abnormal pregnancy. With the hypothesis that an increase in serotonin would reduce volume expansion and cause fetal growth restriction, we evaluated the maternal and fetal effects of the administration of the serotonin precursor 5-hidroxytryptophan (5-HTP) to Sprague-Dawley rats. At pregnancy day 13 (nϭ19) or in random cycle nonpregnant rats (nϭ10), animals were assigned to a single injection of 5-HTP (100 mg/kg IP) or to a control group. Animals were studied at day 21, after overnight urinary collection. Additional pregnant rats received ketanserin (1 mg/kg), a 5-HT 2 receptor antagonist, 1 hour before 5-HTP injection. In pregnant rats, 5-HTP lowered plasma volume (control: 22Ϯ1.1; 5-HTP: 17Ϯ0.7 mL; PϽ0.001) and creatinine clearance, whereas serum creatinine and urinary protein excretion were increased; no changes were observed in nonpregnant rats. Systolic blood pressure did not change significantly. Urinary kallikrein activity and plasma aldosterone levels decreased only in pregnant animals. Fetal (control: 5.5Ϯ0.1; 5-HTP: 4.2Ϯ0.2 g; PϽ0.001) and placental weights were reduced. In nonpregnant and pregnant animals, 5-HTP caused profound renal morphological alterations and decreased kallikrein immunostaining. Preadministration of ketanserin abolished all of the changes associated with the use of 5-HTP. These data indicate that the administration of a serotonin precursor to pregnant rats limits plasma volume expansion and fetal growth via 5-HT 2 receptors, suggesting a possible role for serotonin in abnormal pregnancy. We postulate that an increased vascular resistance, both at the placental and renal levels, mediates these effects. Key Words: preeclampsia/pregnancy Ⅲ experimental models Ⅲ acute kidney failure Ⅲ kallikrein Ⅲ aldosterone Ⅲ plasma volume Ⅲ serotonin N ormal pregnancy, in humans and other mammals, is characterized by a significant reduction in systemic vascular resistance associated with lower arterial blood pressure, increased cardiac output, stimulation of the renin-angiotensin system, and plasma volume expansion. 1-3 These changes cause an important increment in uteroplacental blood flow, allowing normal fetal growth.In previous studies we have observed that pregnancy complications, such as fetal growth restriction or preeclampsia, are associated with reduced plasma volume expansion, increased vascular resistance, and lower levels of plasma renin activity, plasma aldosterone, and urinary kallikrein activity. 4,5 In preeclampsia an increased platelet aggregation has been described, with a consequent increment in serotonin (5-hydroxytryptamine; 5-HT) levels. 6 Serotonin is an endogenous amine synthesized by the enzymes tryptophan hydroxylase and decarboxylase from 5-hydroxytryptophane (5-HTP) and is metabolized by the enzyme monoamino-oxidase A to 5-hydroxyindole-3-acetic acid. 7 Serotonin has multiple cardiovascular effects, causing either blood vessel dilation through its 5-HT 1...

Abstract-Water-retaining hormones are stimulated during pregnancy allowing normal volume expansion. Because pregnant rats actively retain water, we postulate that water deprivation (WD) would cause a greater reduction in plasma volume in pregnant than in nonpregnant rats. To test this hypothesis, Sprague-Dawley pregnant and nonpregnant rats were water-deprived for 48 hours. At day 19 of pregnancy, or in the corresponding day in nonpregnant rats, they were randomly assigned to either a WD or a control (C) pair-fed group (nϭ10 to 12 per group). WD significantly reduced body weight, food intake, and creatinine clearance, and increased urinary osmolality in nonpregnant and pregnant rats. WD reduced plasma volume in a similar proportion in nonpregnant and pregnant rats (nonpregnant rats Cϭ13.1Ϯ0.

The hemodynamic characteristics of 11 normotensive gravidas with idiopathic fetal growth retardation (FGR), were compared with 11 controls of similar age, parity and body size. At weeks 36–38 of gestation, plasma volume was 3,161 ± 121 ml in controls and 2,624 ± 95 ml in the FGR group (p < 0.003); cardiac output (CO) was 6,191 ± 132 ml/min in controls and 5,483 ± 186 ml/min in the FGR group (p < 0.01). Total peripheral vascular resistance (TPVR) was lower in controls than in FGR (1,031 ± 33 vs. 1,306 ± 62 dyn/s/cm⁵; p < 0.001). Birth weight was correlated with both plasma volume (r = 0.61; p < 0.01) and CO (r = 0.53; p < 0.02) and inversely correlated with TPVR (r = ––0.69; p < 0.001). These results are in line with the hypothesis that a reduced plasma volume leads to a lower CO and, secondarily, to reduced uterine blood flow and FGR.