Abstract Body: Women with a history of preeclampsia (hxPE) have a ≥4-fold risk for developing cardiovascular disease compared to matched women who had a healthy pregnancy (hxHC). Angiotensin (ang) II-mediated vasoconstriction contributes to the persistently reduced microvascular function in the years after preeclampsia. Excessive activation of ang II type 1 receptors (AT₁R) is one putative mechanism underlying increased ang II constrictor sensitivity. This may be countered by ang II type 2 receptor (AT₂R) activation; however, the extent that reductions in AT₂R-mediated responses contribute to increased ang II sensitivity after preeclampsia is unknown. Using the cutaneous microcirculation as a model, we hypothesized that 1) AT₂R-mediated dilation is attenuated in hxPE compared with hxHC, 2) AT₁R inhibition improves reduced AT₂R-mediated dilation in hxPE, and 3) AT₂R inhibition would increase ang II-mediated constriction in hxHC but have no effect in hxPE. Nine hxPE (37±5 years) and 9 matched hxHC (34±5 years) within 5 years postpartum had 4 intradermal microdialysis fibers placed in the ventral forearm for the local delivery of pharmacological agents. Two fibers received graded infusions of compound 21 (AT₂R agonist; 10^-14-10^-8mol/L) alone or co-perfused with losartan (AT₁R antagonist; 43µmol/L) for the assessment of AT₂R-mediated dilation. The remaining 2 sites received graded infusions of ang II (10⁻²⁰–10⁻⁴mol/L) alone or co-perfused with PD-123319 (AT₂R antagonist; 1µmol/L) to assess the role of AT₂R in vasoconstrictor sensitivity to ang II. Red blood cell flux was measured directly over each fiber and cutaneous vascular conductance was calculated (CVC=flux/MAP) and expressed as a % maximum (43°C + 28mM SNP) or % baseline. Those with hxPE had attenuated AT₂R-mediated dilation (hxPE: 15±5 vs hxHC: 27±9%max; P=0.01) that was improved with AT₁R inhibition (losartan: 22±7 vs control: 15±5%max; P=0.003). Vasoconstrictor sensitivity to ang II was greater in hxPE compared with hxHC (hxPE: 39±14 vs hxHC: 55±6%baseline; P<0.001). AT₂R inhibition increased the vasoconstrictor response to ang II in hxHC (PD-123319: 39±12 vs control: 55±65%baseline; P<0.001) but had no effect in hxPE (PD-123319: 39±13 vs control: 39±14%baseline; P=0.29). These data suggest that women with a history of preeclampsia have reductions in AT₂R-mediated dilation that contributes to increased ang II vasoconstrictor sensitivity and sustained microvascular dysfunction after preeclampsia.