Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA063

Poster Communications

Elevated angiotensin II during pregnancy promotes renal inflammation in male rat offspring

M. Okuliarova1, P. Svitok1, M. Zeman1

1. Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.

Suboptimal conditions experienced in utero can change the developmental program of an individual and result in an increased risk of cardiovascular diseases in adulthood. However, the potential physiological mechanisms beyond this link are still not recognized. Our previous results indicate that disturbed homeostasis of renin-angiotensin-aldosterone system in rats during pregnancy can lead to increased blood pressure of male progeny in adulthood. To investigate underlying mechanisms between adverse prenatal environment and development of increased blood pressure we analysed effects of sustained infusion of angiotensin II (ANG) in pregnant rats on the adult immune status of male offspring. Female Wistar rats were either sham operated (n=4) or implanted with osmotic minipumps (n=5) continuously releasing ANG II at a dose of 2µg kg-1 h-1 for 14 days from day 6 of pregnancy. A mixture of ketamine (75mg kg-1) and xylazine (10mg kg-1, i.p.) was used as anaesthesia. Progeny of these females was assigned to control (CONT, n=12) and ANG (n=13) rats, respectively. From age 3 till 4 months a half of the animals from each group was fed with an increased-salt diet (0.8% sodium). During this period, immunophenotyping of venous blood and functional analysis of granulocytes were performed by flow cytometry. Finally, rats were killed under CO2 anaesthesia and pro-inflammatory cytokines, tumor necrosis factor alpha (TNFa) and interleukin 6 (IL-6), were measured in the plasma and renal inflammation was evaluated by immunohistochemistry. Reduced numbers of CD8+ T-cells and monocytes were found in circulation of ANG than CONT rats. This corresponded with higher renal infiltration of T-cells and macrophages in ANG as compared to CONT rats. Increased salt intake lowered number of granulocytes and their phagocytic activity in ANG but not in CONT rats. No differences between groups were found in plasma levels of TNFa and IL-6 suggesting that systemic inflammation was not developed at this stage. In conclusion, our results demonstrate changed peripheral and tissue distribution of immune cells in adult male progeny of female rats with experimentally elevated ANG II levels during pregnancy. Increased immune cell infiltration in the kidney of ANG rats indicates development of renal inflammation, which in turn may link adverse prenatal environment with altered cardiovascular functions in adulthood.

Where applicable, experiments conform with Society ethical requirements