Physiol. 43): H1605-H1612, 1998.-To assess the contribution of the arterial and venous systems in the hemodynamic changes of normal pregnancy, we studied blood flow, vascular resistance, venous tone, and the viscoelastic properties (''creep'') of the upper and lower limbs (using plethysmography), aortic distensibility (using pulse wave velocity measurements), and cardiac dimensions (using echocardiography) in nine healthy women. Studies were longitudinally performed at the first (10-13 wk) and third (33-38 wk) trimesters of pregnancy in comparison with the period between the third and sixth month after delivery. From the first trimester, heart rate significantly increased while systemic blood pressure and limb vascular resistances did not change significantly and aortic distensibility increased (P Ͻ 0.05). Lower limb viscoelastic properties decreased at the third trimester (P Ͻ 0.05) and venous tone increased from the first trimester (P Ͻ 0.01), whereas little changes were observed at the site of upper limbs. The decrease in calf venous tone was significantly correlated with the increase in left ventricular diastolic diameter at the first (P Ͻ 0.001) and the third trimester (P Ͻ 0.05). The study provides evidence that during normal pregnancy, changes in the arterial and venous sides of the circulation occur independently of pressure alterations. The increase in venous tone, contributing to preload augmentation, and the decrease in aortic stiffness, reducing afterload, both optimize cardiac function until delivery. venous tone; aortic compliance; arterial distensibility; cardiac function IT IS WELL ACCEPTED that a normal pregnancy is characterized by a large increase in total blood volume and in cardiac output (31,32,48). Blood volume expansion appears early during the pregnancy and rises up to 50%. Cardiac output rises up to 40-50% above nonpregnant values, and the highest increase is reached halfway through gestation. Cardiac output is the product of heart rate and stroke volume. Heart rate is known to reach a 10-27% increase between weeks 4 and 36 of pregnancy (10). However, an increase in stroke volume might also play an important role at the early phase. Stroke volume appears elevated at least until weeks 28-32 (31). The mechanism(s) causing the increase in stroke volume are not yet well established. In pregnant rats and women, an increased cardiac contractility has been suggested (13,36,44), but the differentiation between the contractile properties of cardiac muscle itself and the contractile changes that result from altered preload and afterload is difficult to establish. The possibility should be considered that an increase in venous return also plays a major role. In the literature, numerous data indicate a significant increase in venous capacitance (11,17,18,28,35,47). However, significant discrepancies have also been reported, depending mainly on the site of measurement of venous variables (40, 46). Furthermore, the early venous changes could not be adequately detected because pregnant women were not ...

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Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored. This was an open, non-randomized study, each patient serving as her own control. For 3 patients, we aimed to determine the possible transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and data were analysed by noncompartmental linear pharmacokinetic methods. The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10-20%).

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