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 (similar to 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 (similar to 25%; P<0.01) with an accompanying reduction in placental weight, and at gestational age day 28, volume density of fetal capillaries was increased (similar to 22%; P<0.05). Placental renin mRNA was lower in both the 2K-1W (similar to 88%) and 2K-2W (similar to 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 (similar to 36%) and 2K-2W (similar to 31%) groups at gestational age day 14 and greater (similar to 36%) in the 2K-2W group at gestational age day 21 (all P<0.01). Associations between placental AT(1)R and AT(2)R 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. J Hypertens 28:959-968 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.