Publications & Reports

Role of inflammation and the angiotensin type 2 receptor in the regulation of arterial pressure during pregnancy in mice.

Katrina M Mirabito, Lucinda M Hilliard, Zihui Wei, Chris Tikellis, Robert E Widdop, Antony Vinh, Kate M Denton
From the Department of Physiology (K.M.M., L.M.H., K.M.D.) and Department of Pharmacology (Z.W., R.E.W., A.V.), Monash University, Clayton, Victoria, Australia; and Baker Medical Research Institute, Melbourne, Victoria, Australia (C.T.).


During normal pregnancy the renin-angiotensin system is activated, yet pregnant women are resistant to the pressor effects of angiotensin II. Our aim was to determine the role of the angiotensin type 2 receptor (AT2R) in the regulation of arterial pressure, natriuresis, and immune cell infiltration during pregnancy. Mean arterial pressure was measured via telemetry, and flow cytometry was used to enumerate immune cell infiltration in 14-week-old wild-type and AT2R knockout mice during gestation. In wild-type mice, mean arterial pressure decreased during gestation, reaching a nadir at gestational day 9 (-6+/-2 mm Hg) and returned to near preconception levels during late gestation. In AT2R-deficient mice, the midgestational decrease in mean arterial pressure was absent. Furthermore, mean arterial pressure was significantly increased during late gestation compared with wild-type mice ( approximately 10 mm Hg). As expected, circulating immune cell activation was suppressed during pregnancy. However, this response was absent in AT2R-deficient mice. While renal immune cell infiltration was similar between the genotypes, there was a significant T cell phenotypic switch toward a proinflammatory T-helper 1 phenotype in AT2R-deficient mice. These data indicate that the AT2R plays an important role in arterial pressure regulation and may modulate T cell activation and renal cytokine production during pregnancy. Therefore, deficits in AT2R expression may contribute to pregnancy-induced hypertension and thus represents a potential therapeutic target.


  • Journal: Hypertension
  • Published: 01/09/2014
  • Volume: 64
  • Issue: 3
  • Pagination: 626-631