Fetal growth and well-being in a study of maternal hypertension in rabbits.

Obtaining growth and physiologic data in the postnatal laboratory animal is common. However, monitoring growth in utero is far more difficult, with little data available except upon termination of pregnancy. High-resolution ultrasound was used to monitor growth, morphology, and fetal well-being in normotensive and hypertensive rabbits (21 fetuses) at day 16, 20, and 26 of the 32 day gestational period. Set protocols, comparable to those routinely assessed in humans, were devised and followed for each examination. Birth weight was greater in offspring of hypertensive as compared to normotensive mothers (p < 0.001); however, litter size was reduced. The greater birth weight was reflected in growth parameters measured throughout gestation indicating the predictive value of ultrasound. High-resolution ultrasound was a reliable and sensitive method for biometric and morphologic assessment of the fetal rabbit, demonstrating that growth trajectory of offspring of hypertensive mothers may be altered early in gestation.

Chronic maternal hypertension affects placental gene expression and differentiation in rabbits.

BACKGROUND: Previously, we have shown that adult offspring from hypertensive rabbits develop hypertension. METHOD: We aimed to determine the effects of mild (+15 mmHg) and moderate (+25 mmHg) increases in maternal blood pressure and plasma renin activity on placental differentiation and expression of components of the renin-angiotensin system and 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA in rabbits. Placentas were collected from normotensive (sham), mild (2-kidney-1-cellophane wrapped; 2K-1W) and moderate (2-kidney-2-cellophane wrapped; 2K-2W) hypertensive groups at gestational age of 14, 21 and 28 days. Placental gene expression was quantified by reverse transcriptase-PCR, and morphometry was assessed by videoimage analyses of placental sections. RESULTS: Fetal weight was similar between groups across gestation. In the 2K-1W group at gestational age day 14, fetal-to-placental weight ratio was increased (approximately 34%) as were volumes of fetal capillaries ([up arrow]56%) and maternal blood space at gestational age day 21 ([up arrow]55%) compared with sham (all P < 0.05). In the 2K-2W group, fetal-to-placental weight ratio was increased at gestational age day 21 (approximately 25%; P < 0.01) with an accompanying reduction in placental weight, and at gestational age day 28, volume density of fetal capillaries was increased (approximately 22%; P < 0.05). Placental renin mRNA was lower in both the 2K-1W (approximately 88%) and 2K-2W (approximately 98%) groups at gestational age day 28 (all P < 0.01). Placental 11[beta]-hydroxysteroid dehydrogenase type 2 mRNA was lower in the 2K-1W (approximately 36%) and 2K-2W (approximately 31%) groups at gestational age day 14 and greater (approximately 36%) in the 2K-2W group at gestational age day 21 (all P < 0.01). Associations between placental AT1R and AT2R mRNA and placental differentiation were disturbed by hypertension. CONCLUSION: Mild and moderate maternal hypertension differentially alters placental structure and gene expression that may affect placental functional capacity and contribute to programming of hypertension in offspring.

Chronic maternal hypertension characterized by renal dysfunction is associated with reduced placental blood flow during late gestation in rabbits.

Maternal hypertension associated with renal disease is a common pregnancy complication. Previously, we have shown in a rabbit model of mild hypertension that offspring from hypertensive mothers have increased blood pressure as adults. In human pregnancy, hypertension has been associated with decreased utero-placental blood flow. The aim of this study was to determine placental blood flow (PBF) in mild (2-kidney-1-wrapped; 2K-1W) and moderate (2-kidney-2-wrapped; 2K-2W) rabbit models of maternal hypertension. We hypothesized that PBF would be inversely related to the severity of the hypertension. PBF and renal blood flow (RBF) were measured using microspheres on day 28 of a 32-day gestation, in normotensive (sham), 2K-1W, and 2K-2W hypertensive groups. Mean arterial pressure (MAP, approximately 7 mmHg, P < 0.05) was increased, and RBF ( approximately 35%, P < 0.05) was reduced in the 2K-1W and 2K-2W (MAP approximately 20 mmHg, P < 0.01; RBF approximately 53%, P < 0.05) groups compared with the sham group. In the 2K-1W group, PBF fell by approximately 12% (P = 0.08) and fetal-to-placental weight ratio increased by approximately 12% (P < 0.01) compared with the sham group, reflecting an increase in the functional capacity of the placenta to deliver nutrients to the fetus. In the 2K-2W group, PBF decreased approximately 51% (P < 0.05) compared with the sham group, without changes in placental efficiency. Thus, in late gestation, placental blood flow was significantly reduced in the moderate hypertension group, without accompanying changes in fetal or placental weight or placental efficiency. In contrast, mild hypertension resulted in an increase in placental efficiency, without significant changes in placental blood flow. These findings suggest that mild and moderate hypertension may alter placental delivery of nutrients via differing mechanisms dependent upon the severity of the hypertension.