Role of the AT2 receptor in modulating the angiotensin II contractile response of the uterine artery at mid-gestation

Introduction: During human pregnancy, circulating concentrations of components of the renin-angiotensin system increase, but pressor refractoriness to angiotensin II (Ang-II) is observed. Given the importance of the Ang-II pressor response in deciding susceptibility to preeclampsia and of the Ang-II system for controlling uterine vasoreactivity, we sought to address the effects of pregnancy on the reactivity of the isolated uterine artery (UA) in mice. Materials and methods: Blood pressure was measured throughout pregnancy in awake C57BL/6J mice. UA segments were isolated from three groups of animals (non-pregnant, mid [day 12-13] and late [day 18-19] gestation) and studied by wire myography. Results: UA diameters, KCl-mediated responses, and acetylcholine-dependent vasorelaxation were greater at mid and late gestation than in non-pregnant animals. Ang-II responses were also greater during pregnancy, with an increased contraction in response to AT2 receptor blockade at mid-gestation. AT1 receptor blockade abolished the Ang-II response in all groups. Conclusions: Study findings are consistent with the possibility that AT2 receptor-mediated vasodilatation plays a role in modulating Ang-II contractile responses in pregnancy.